Is the long COVID just another form of chronic fatigue?
CLEVELAND, Ohio – As scientists struggle to unravel the mystery long COVID, it is hard to ignore that most of those who suffer from it share in common symptom – debilitating fatigue.
Researchers are evaluating it as much as 85% of those with long-term COVID experience terrible fatigue that leaves them unable to work or manage even simple daily tasks. Even showering, some patients say, is simply too taxing.
What many people may not realize is that long before COVID, some patients reported the same symptoms of persistent, debilitating fatigue, brain fog, muscle pain, and exercise intolerance, following various illnesses, injuries, or infections. These conditions are collectively called chronic diseases associated with infection and include myalgic encephalomyelitis/chronic fatigue syndrome. But until recently they were largely dismissed by the medical community, which devoted few resources to understanding their cause.
Then came COVID and science began to pay more attention.
“Over the past decade, most well-studied viral or bacterial pathogens have been associated with the development of chronic symptoms in a subset of infected patients.” he said Amy Proalmicrobiologist at PolyBio Research Foundation in conversation with Global Center for Interdependence. She listed syndromes arising from the Ebola, Zika and Dengue viruses, among others, including ME/CFS. Long COVID is believed to be the latest on that list, and patients and doctors are hoping that increased investment in understanding and treating long-term COVID will pay off for those other chronic post-infection diseases as well.
“While the development of long-lasting COVID is sometimes framed as novel or mysterious, it is actually a well-recognized phenomenon,” Proal said.
The disease is largely ignored
Despite the fact that a 2015 Institute of Medicine Report With an estimated 836,000 to 2.5 million Americans suffering from myalgic encephalomyelitis/chronic fatigue syndrome, the community of doctors and researchers who study and treat the disease and the vast majority of their patients were hardly taken seriously before the pandemic. Patients were told that their symptoms were all in their heads, they lacked motivation, or even that they would feel better if they just started exercising more.
Part of the problem is the lack of medical education dedicated to this disorder. Less than one-third of medical schools include information specific to ME/CFS, and only 40% of medical textbooks include information about the condition, according to The IOM report, which goes on to state that there is “a lack of understanding of the diagnosis and treatment of this condition among health care professionals and skepticism about whether it is actually a true medical condition…Many providers believe that it is a psychiatric/psychological illness or at least has psychiatric/psychological component. “
New virus, same disease?
For most of its history, ME/CFS did not have a clear definition and diagnostic criteria. There just wasn’t a single theory about what was going on. The result was a lack of support from the medical and scientific community, which financially tied researchers’ hands and left patients struggling. to confirm theirs symptoms.
But the advent of long-term COVID began to change all that. Waves of people suddenly reporting identical symptoms and the sheer scale of the problem quickly brought the urgency of a solution into sharper focus and prompted the US government to commit billions of dollars to understanding the disease and developing potential therapies.
The many parallels between prolonged COVID and ME/CFS have led some to wonder whether prolonged COVID is just another form of post-infectious fatigue, but one with a clear cause and millions of potential research subjects.
For those who have devoted their lives to unraveling the mystery of ME/CFS, this is a huge boon to research and an opportunity to finally uncover the biological basis of a disorder that has so far eluded them.
“The most constructive thing that could come out of long COVID is that a very large investment in research will teach lessons that will apply beyond long COVID to ME/CFS, other post-infectious and post-injury syndromes, and maybe even wider.” he said a long time COVID researcher Anthony Komaroff, from Harvard Medical School.
The brain’s protective system has broken down
According to Komaroff, there is now strong evidence that the flu-like symptoms of fatigue, muscle aches, brain fog, and loss of appetite shared by ME/CFS and long-term COVID patients are actually a built-in response in humans to conserve energy during period of illness or injury.
“When you are infected or injured, your immune system is activated to fight the infection and heal the injury. It takes a lot of energy to do that, and your body only has so many energy molecules available,” Komaroff said. Under normal circumstances, he said, this reaction is protective, but with long-term COVID or ME/CFS, patients continue to experience symptoms months or years later, long after the infection is believed to have cleared.
Five years ago, Komaroff proposed the theory that this so-called “fatigue response” is the result of the activation of a few specific and very tiny groups of neurons “whose sole purpose in life is to cause that set of symptoms when you get sick,” he said.
These groups of neurons are located in a part of the brain called the hypothalamus, and another area called the brainstem, areas that were already known to regulate sleep, mood and appetite. Komaroff said neurons sit in the brain resting until disease or injury stimulates them and causes this orchestrated set of symptoms.
“It was a nice theory, but there wasn’t a shred of evidence to support it yet a year or two ago,” Komaroff received.
But then four separate papers were published in the journal Nature, the the latest September, showing that such clusters of neurons not only exist in the brains of mice, but when stimulated can produce disease symptoms.
Although he acknowledges that the findings were in rodents, not humans, he is encouraged. “Most things we hold to be true of a mouse brain, the same is true for humans,” Komaroff said. “It’s going to be a while before we can prove that.”
The role of inflammation
But if Komaroff’s theory is correct, it also raises the question of why, after the infection clears, some people continue to experience these symptoms much later. Why does the brain still think it has to protect you if the infection is gone?
Komaroff believes inflammation has something to do with it.
“We know that if, for example, you have inflammation in the lining of your gut, signals travel up the vagus nerve to your brain and activate the brain’s immune system,” he said. “It basically tells the brain that there is a threat somewhere else in the body and you need to prepare for it.”
What is not known is the source of that inflammation; is it a residual effect The COVID virus remains hidden in various tissues of the bodywhether it is the result of COVID activating other latent viruses such as Epstein-Barr or herpes, or whether the body’s natural balance of viruses and bacteria is thrown off and the immune system creates inflammatory molecules even in the absence of a threat.
It could be any of those things, or all of them, Komaroff said.
“It’s unlikely that it’s exactly the same process in every person,” he said. “All these things are not only plausible, but probable.”
And this is what makes understanding long-term COVID and ME/CFS so challenging right now. The researchers identified seven factors, which are not mutually exclusive, that can contribute to their development.
“They are all connected, and patients can have one or more problems occurring at the same time,” Proal said. “…But we don’t necessarily think that exactly the same thing happens to every patient.”
Researchers are already looking for biomarkers that can be used to identify and diagnose patients with long-term COVID and ME/CFS, and different research groups are exploring different treatment options. Some suggest antiviral treatments that target potential reservoirs of the virus that may still be present in the body or brain. Others, Komaroff said, are proposing treatments that can calm the immune activation in the brain that triggers the fatigue response.
It remains to be seen which, if any, of these treatments actually improve symptoms. Those results are still many months or years away, but Komaroff believes the answers are coming.
“I’m a big believer in that,” he said. “I just think you have to be realistically patient.”
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