A new review article, spearheaded by researchers from Johns Hopkins University School of Medicine, asserts the increasingly prominent condition known as long COVID shares significant physiological similarities to chronic fatigue syndrome. The researchers say a better understanding into the overlap between both illnesses can inform therapeutics in the future for many kinds of post-viral illnesses.
Early in 2020, a few months into the pandemic, doctors started to notice some COVID-19 symptoms lingering in otherwise completely recovered patients. These symptoms were diverse, spanning everything from sexual dysfunction to bladder issues, but most patients shared several common features – fatigue, brain fog and reductions in exercise capacity.
The condition was dubbed long COVID, and more recently labeled clinically as PASC (Post-Acute Sequelae of SARS-CoV-2 infection). The research so far suggests between 10 and 30 percent of those suffering mild COVID-19 can experience lingering symptoms for months. Up to three-quarters of severe hospitalized patients report persistent symptoms.
Until relatively recently chronic fatigue syndrome (CFS) was stigmatized as more of a psychological condition than a physical one. Also known as myalgic encephalomyelitis (ME), and generally referred to under the umbrella term ME/CFS, it is now commonly accepted as a real chronic disease, however, its origins are still unclear.
Up to 2.5 million people in the United States are thought to suffer from ME/CFS. For many sufferers the condition appeared quickly, out-of-the-blue, following some kind of acute viral infection.
“… many cases of post-infectious fatigue follow in the wake of acute infections that are not known to cause permanent damage to the heart, lungs or kidneys – and in people without comorbid PTSD or depression,” write ME/CFS researchers Anthony Komaroff and Lucinda Bateman in a long COVID article published in early 2021. “In the typical case of ME/CFS, in particular, the inciting 'infectious-like' illness most often appears to be a transient infection, or a primary infection that becomes permanent but does not typically produce chronic organ dysfunction (such as occurs with Epstein-Barr virus).”
Considering how little is known about ME/CFS it would certainly be premature to claim the illness is the same as long COVID, but a new article published in Proceedings of the National Academy of Sciences is suggesting there is evidence the two conditions share similar biological abnormalities.
“The body’s response to infection and injury is complex and covers all body systems,” explains lead author on the new article, Bindu Paul. “When that response is in disarray – even just one aspect of it – it can cause feelings of being tired, brain fog, pain and other symptoms.”
Paul and colleagues point out in the article that acute cases of COVID-19 and patients with ME/CFS both display signs of what is called redox imbalance. This condition involves an imbalance between reactive oxygen species (which can include free radicals) and antioxidant defense mechanisms inside cells. Excessive volumes of reactive oxygen species can damage cellular components and induce production of inflammatory molecules.
The hypothesis presented in the article is that this redox imbalance leads to systemic inflammation and neuroinflammation which accounts for many symptoms seen in both long COVID and ME/CFS. The researchers are cautious to note this redox imbalance hypothesis is not presented as the singular cause of both conditions but instead offers directions for investigators to begin looking at future treatments.
“Clearly, COVID-19–induced permanent damage to the lungs (chronic hypoxia), heart (congestive failure), and kidneys (fluid and acid-base abnormalities) could cause some of the persisting symptoms seen in long COVID-19,” Paul and co-authors write in the new article. “In both long COVID-19 and ME/CFS other symptoms (e.g., fatigue, brain fog) may be generated by neuroinflammation, reduced cerebral perfusion due to autonomic dysfunction, and autoantibodies directed at neural targets …”
Paul and colleagues note there are a number of current treatments attempting to address redox imbalances. Some are being tested to treat acute hospitalized COVID-19 patients, and others have been trialed to improve symptoms of fatigue on ME/CFS patients. None have so far proved extraordinarily effective, and the researchers suggest the heterogenous nature of redox imbalance may make it a challenging therapeutic target.
"In general, however, oral therapies directed at restoring redox balance have not produced dramatic improvements in conditions associated with redox imbalance," the researchers write in the article. "No single antioxidant can scavenge or neutralize the wide variety of ROS and RNS singlehandedly. Hence, up-regulating pathways that counteract multiple abnormalities and bolster antioxidant defense and balance may be more beneficial. The timing of intervention may also be critical."
In general, post-viral illness is a remarkably understudied field and growing concerns over long COVID offer the biggest research boost on the topic in decades. Mady Hornig, a ME/CFS researcher from Columbia Mailman School, welcomes the long-overdue attention and suggests insights gleaned from novel studies into long COVID could hopefully lead to new treatments for all kinds of post-viral illnesses.
“One of the interesting things we’ve seen so far is that some COVID-19 patients who initially seem to be on the path to developing ME/CFS actually start to feel better after four or five months,” says Hornig. “We think that looking closely at these people and comparing them to others who eventually do get diagnosed with ME/CFS could yield valuable insights. Might there be something distinct about their immune systems that makes them more resilient? That could be the kind of discovery that opens up new possibilities for treatment.”
The new review article was published in PNAS.
Source: Johns Hopkins Medicine
