“It’s kind of like in Harry Potter, when the dementors come and they suck away all of your energy,” says Kathleen Dennis, a former Toronto health-care worker living with a condition called myalgic encephalomyelitis, or ME/CFS.
ME/CFS is a misunderstood complex multi-system chronic illness usually triggered by a viral or bacterial infection. It’s estimated to affect more than 600,000 Canadians, making it more common than breast cancer, Parkinson’s disease and multiple sclerosis combined. Though not exclusive to COVID-19, the pandemic has exacerbated the situation as more people become infected, and re-infected.
ME/CFS’s hallmark symptom, post-exertional malaise (PEM), also known as post-exertional symptom exacerbation, can affect people differently, but is generally defined as the worsening of symptoms after even minor physical or mental activity. Symptoms triggered by PEM can start 12 to 48 hours after exertion and leave even mild and moderately ill patients bedridden with debilitating “crashes” that can last for weeks or months at a time.
“For me it feels like a combination of being hit by a bus and somebody kneeling on my chest,” Dennis says. “Then it literally feels like all the tendons, bones, muscles and blood are being sucked out of my body.”
During the height of her career, Dennis travelled the world working with organizations like Doctors Without Borders. Then in 2012, she contracted West Nile virus in her Toronto backyard – an irony she says is not lost on her. The infection was followed by myriad debilitating symptoms, including extreme physical and cognitive fatigue, musculoskeletal pain and poor sleep. After six years of declining health and setbacks from a respiratory infection, Dennis was finally diagnosed with ME/CFS in 2018 after her illness forced her to stop working. “I had such bad muscle weakness. I couldn’t even use a knife to cut my food,” she says.
Despite its prevalence and life-limiting symptoms, ME/CFS is unlikely to be found in most medical school textbooks or curriculums across the country. Research has been underfunded and for decades the illness has been largely dismissed as psychiatric in nature. Women make up roughly 80 per cent of those with the illness, which experts say has likely contributed to its stigmatization and general dismissal.
For decades, official guidance in Canada has recommended exercise and cognitive behavioural therapy to treat ME/CFS. Researchers have now confirmed what many patients have voiced for decades: exercise actually causes ME/CFS symptoms to worsen, often leading to significant and disabling setbacks. The National Institute for Health and Care Excellence (NICE) in the U.K. only revoked their recommendation for clinical guidance for a treatment known as graduated-exercise therapy in 2021, after years of patient advocacy.
There is currently no known cure for ME/CFS. And with the exception of a handful of specialists scattered throughout the country, little meaningful support for patients outside of online peer-support groups.
But research interest in ME/CFS and other similar illnesses is growing as post-viral conditions have become even more common during the pandemic. Recent reports show that in Canada, 30 to 40 per cent of patients who were not hospitalized from SARS-CoV-2 experience symptoms 12 weeks post-infection. A further 10 to 30 per cent of those infected with SARS-CoV-2 report persistent neurological and other symptoms after six months. A recent study found that 58 per cent of long COVID patients surveyed met the scoring threshold for PEM, meaning more than half of those with long COVID meet the diagnostic criteria for ME/CFS and suggesting that in many instances, these illnesses are likely one in the same.
More than half of those with long COVID meet the diagnostic criteria for ME/CFS.
Alain Moreau of the Open Medicine Foundation has been working to answer some of the biggest unknowns about complex chronic illnesses. Moreau is also a part of ICanCME research network, a group aiming to fill research gaps in ME/CFS, attract more research interest and offer grant opportunities. Dennis is among a dedicated group of ME/CFS patients who have been working with Moreau on the frontlines of this research.
The research Moreau and his team in Montreal have generated over the last two years in particular signal hope for ME/CFS and long COVID sufferers alike.
Moreau and his team began cataloguing biomarkers in patients with ME/CFS using an innovative method that evokes PEM for measurement. Using a cuff that applies gentle pressure for 90 minutes, Moreau’s researchers induce a controlled PEM response in some of the most severe ME/CFS patients. “For a normal person, it would just feel like a gentle massage but for someone with severe ME/CFS, 90 minutes of stimulation on the upper arm would feel like running a marathon.” The longitudinal study measures several physiological changes including heart rate, respiration and impact on sleep, as well as other biomarkers such as urinalysis and protein level in plasma.
The results have been significant.
“From that, we were able to identify who has ME/CFS, and also further stratify into four clusters that predict disease severity,” Moreau says. He theorizes that ME/CFS exists on a spectrum that we can objectively measure even though it has many different triggers in addition to a number of overlapping co-morbidities like fibromyalgia, mast cell activation syndrome and postural tachycardia syndrome.
Moreau’s research takes a close look specifically at the role of microRNA, a family of molecules that helps cells control the kinds and amounts of proteins they make. Moreau says microRNA are becoming increasingly popular in medicine, not only in detecting but staging disease to determine its extent and course of treatment, for example using liquid biopsies in oncology. For his purposes, Moreau uses microRNA to determine genetic differences between different ME/CFS patients and has created diagnostic testing that can differentiate ME/CFS from other similar illnesses.
“We found that by looking at these panels of 11 microRNA, you can pinpoint a specific target that may explain something like physical and mental fatigue and other dysfunctions that affect the mitochondria and create sleep disturbances,” Moreau says.
Stratifying different subgroups within the larger umbrella diagnosis of ME/CFS is about building an empirical foundation for measuring the illness that hasn’t existed before, Moreau says. This will allow more researchers to gain footing in the field and produce effective clinical trials. It will also help address some of the most glaring issues in research funding.
“We need to understand and identify actionable therapeutic targets where we can reposition drugs, or at least define a more mechanistic approach,” he says. Without this knowledge, it’s really difficult to design a viable clinical trial and to attract pharmaceutical biotechs to the field.
“With these biomarkers we can predict who might respond well to certain kinds of treatment and who would not. If we can show (pharmaceutical companies) that we can pinpoint a group or subgroup of patients that could benefit from a certain type of therapy, they’ll be more likely to invest.”
Moreau’s team is currently working on a single blood test that would be able to differentiate patients with ME/CFS from those with fibromyalgia and indicate who has one or both conditions.
Moreau’s work is also moving to include the application of these biomarkers to long COVID.
“I really want to build a foundation of solid science, so we know how to target the most debilitating symptoms. That’s why we need to engage in the field of precision medicine for ME,” says Moreau.
While ME/CFS patients like Dennis have lived unaided with post-viral illnesses for decades, Dennis says that she sees the emergence of long COVID as a sort of “terrible silver lining.”
“We still have a long way to go, especially in Canada,” she says. “But I think (the pandemic) will make a big difference. There’s no doubt that we are starting to hear physicians and researchers use the terms ME and long COVID together now.”
Says Moreau: “The COVID-19 pandemic has unfortunately created this huge opportunity. Let’s leverage that for the sake of millions of individuals.”