This is the beginning of a series of blogs that will attempt to keep up on long-COVID research and its possible applications to chronic fatigue syndrome (ME/CFS), dysautonomia, fibromyalgia (FM), and related diseases.
These blogs are being done with the recognition that much (much) more money, energy, talent, and resources are going to be devoted to understanding long COVID over the next couple of years than have been spent on ME/CFS or FM in their entire history. They’re being done out of the possibility that this research will actually get to the bottom of what’s happening in long COVID, ME/CFS, and possibly even fibromyalgia.
The series is being started with the anticipation that at some point it’s going to be very hard to keep caught up with long COVID research.
We’re not there yet. With this early taste of long-COVID research studies, though, we’re getting a foreshadowing of what will come. With regard to epidemiology – the attempt to understanding who, how many, and what kind of people come down with long COVID – even at this very early stage, we’re seeing studies whose sizes dwarf anything we’re used to seeing in ME/CFS or FM.
One of the studies getting underway, for instance – the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) – which contains over 100 researchers, will include within it 14 already established prospective cohort studies. These studies are already following the health of large populations in detail. By piggybacking on them, the C4R study should be able to determine what kind of person gets long COVID, what kind of long COVID they get, etc.
An almost 1,000-person healthcare worker study found that 32% were experiencing difficulty coping 3 months later, with fatigue being the most troubling symptom. A 6,000-person survey found six months later that 2.2% were experiencing long-COVID symptoms.
Links to ME/CFS Strengthen
Leonard Jason’s epidemiological study found that, over time, the core symptoms in ME/CFS are becoming more and more prominent in long-COVID patients. Similarly, a review of long-COVID studies concluded that:
“Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS.”
A systematic overview of 45 reviews suggested that two kinds of long COVID are emerging, neurologically: a life-threatening one similar to Guillain-Barre Syndrome, encephalitis, and one similar to chronic fatigue syndrome.
A Fibromyalgia / Chronic Pain Long-COVID Connection
Some people with fibromyalgia may be under the impression that long-COVID research will not benefit them much. The death of Heidi Ferrer, a Dawson’s Creek writer, and long-COVID patient, who took her life after a year of excruciating physical pain that left her unable to sleep, underscores the fact that the connection between long COVID, chronic pain, and diseases like fibromyalgia is very real indeed.
Pain is showing up in the epidemiological studies. One 1,200-person study found that seven months after long COVID, people with a pre-existing pain condition tended to be worse off, and that 38% of the entire sample experienced increased musculoskeletal pain.
A Veterans Affairs study echoed that finding and made a different kind of news when it reported that in the six months following “recovery” from COVID-19, long-COVID patients were at a higher risk of death. They were also coming down with a wide range of disorders – many of which could be associated with ME/CFS and/or FM. The disorder list included nervous system, neurocognitive, metabolic, cardiovascular, and gastrointestinal disorders. Pain and fatigue were two of three main symptoms (malaise, fatigue, musculoskeletal pain), the study found.
The Subsetting Begins
A retrospective study presented something that we will surely see in spades over time – the attempt to subset long-COVID patients.
The Harvard study, “Evolving Phenotypes of non-hospitalized Patients that Indicate Long Covid“, assessed the diagnostic records of 57,000 non-hospitalized patients who’d tested either positive or negative for the coronavirus. It found that most long-COVID patients were under 65, and that a chronic fatigue syndrome-like condition was one of five disease conditions found. (The others were loss of smell or taste, hair loss, and chest pain.)
On a more personal note, a study titled “Reluctant pioneer” described the the difficulty getting medical care and the feeling of being “let down” by their peers that 13 doctors with long COVID experienced.
Low Energy (Hypometabolic) Brain Regions Found
Only a few long-COVID brain studies have been done but they’ve have produced some early and surprising possible connections. One Italian PET/CT scan study found evidence of hypometabolism (reduced energy production) in the thalamus, brainstem, and right parahippocampal gyrus. The study noted, interestingly, that some of the areas of the brain that were demonstrating hypometabolism were found to exhibit hypermetabolism during the infection – suggested that inflammation during the infection may have caused some damage.
Three French studies have found evidence of hypometabolism in the limbic system (thalamus, amygdala), the brainstem, and the cerebellum. One study reported that these clusters of hypometabolic activity were “highly discriminant”; i.e. they accurately described 100% of the patients relative to the healthy controls.
Different symptoms were associated with reduced metabolic activity in different parts of the brain; i.e. pain was associated with reduced activity in the prefrontal cortex, brainstem, and cerebellum. As the authors noted, reduced prefrontal cortex activity has shown up in fibromyalgia (and ME/CFS). It’s a frequent target of repetitive transcranial stimulation in fibromyalgia and is being targeted in ME/CFS now.
Insomnia was associated with the hypometabolism of the brainstem and cerebellum – which the authors suggested was causing dysautonomia. Autonomic nervous system problems, in turn, have been associated with poor sleep in both ME/CFS and fibromyalgia.
Another French study found widespread areas of hypometabolism and “lasting prefrontal, insular and subcortical (limbic) regions, problems with attention, executive functioning” (organizing, planning, etc.) as well as symptoms of anxiety and depression six months after the infection.
Finally, a Malaysian researcher proposed that hypometabolism in the brainstem lies at the heart of long COVID.
One suspects we haven’t seen anything yet. Thus far, studies indicate that long COVID is real and persistent, that a significant subset of long-COVID patients have something akin to ME/CFS and/or fibromyalgia, and most interestingly, that widespread hypometabolism in the brain may be present, and that similar parts of the brain – the prefrontal cortex, the limbic system and the brainstem – may be involved.
Time will tell if these findings hold up, but it’s certainly striking to see hypometabolism show up so early in long COVID.
We’re still in the very early days yet. Immune studies, metabolic studies, more brain scans, etc. hopefully are just around the corner.
A Solve M.E. funded project to uncover and assess the latest Long COVID research made these blogs possible