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“It’s all in your head”: what long-COVID research has taught us about chronic fatigue syndrome
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Original Medthority Content

“It’s all in your head”: what long-COVID research has taught us about chronic fatigue syndrome

Read time: 10 mins
Last updated:16th Aug 2022
Published:16th Aug 2022
Author: Article by Elizabeth Donald, BmedSci, MSc

Article by Elizabeth Donald, BmedSci, MSc.

Among the spectrum of confounding SARS-CoV-2 (COVID-19) symptoms is the persistence of phenomena labelled long-COVID. Defined by a constellation of persistent long-term symptoms ranging from mild to debilitating including fatigue, depression, memory impairment and poor concentration, long-COVID has been compared to a condition known for decades: chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)1. Already a contentious and hotly debated issue among the medical community, tensions have now resurfaced around CFS/ME with the race to understand the origins of post-COVID sequelae.

CFS/ME is a complex long-term illness often triggered by an acute viral infection with a wide range of symptoms that can have a significant effect on daily activities, the most common being extreme fatigue1.

CFS/ME affects up to 250,000 people in the UK and an estimated 17 million worldwide, however up to 90% of sufferers remain undiagnosed2

The failure to identify a specific causative agent coupled with a lack of any abnormal, routine clinical laboratory test results has led many healthcare practitioners (HCPs) to conclude that CFS/ME lacks a pathophysiological basis and must therefore be of psychosomatic origin3.

Because of this lack of knowledge, many people suffering with CFS/ME have their symptoms dismissed as a psychological condition (ie ‘illness beliefs’), and are prescribed a combination of exercise, cognitive behavioural therapy and mindfulness, with limited success4-6.

...It is vastly easier to dismiss an illness as imaginary than to grapple with brain physiology.
Dr David Bell, member of the Scientific Advisory Board of the Open Medicine Foundation and CFS/ME researcher.

This “all in your head” myth of CFS/ME has permeated medical discourse and popular culture, with destructive consequences for the millions of people living with the condition. In fact, patient surveys consistently report that people with CFS/ME encounter importunate medical scepticism, difficult interactions with HCPs and poor-quality care7. Forced to fend off accusations of laziness and hypochondria, people are left feeling vulnerable, alienated, and disillusioned with the healthcare profession.

As Jennifer Brea, a long-term sufferer of CFS/ME puts it, “Sickness doesn't terrify me and death doesn't terrify me. What terrifies me is that you can disappear because someone is telling the wrong story about you. I feel like this has happened to all of us living this.”

However, there is a silver lining. As a stream of novel research into chronic post-viral illness saturates the sphere of science and medicine, CFS/ME is gaining new respect. Long-COVID and CFS/ME are both considered post-viral syndromes with similar pathogenesis and patterns of neurological degeneration, secondary to viral infection.

They are the same disease — or very, very similar.
Dr Liisa Selin, viral immunologist and professor at UMass Chan Medical School.

The latest research into the neurological effects of COVID-19 on the brain shows that there is a significant reduction in grey matter mass8, coupled with widespread neuroinflammation and evidence of oxidative stress9-12. One study found evidence that antibodies produced in response to COVID-19 may mistakenly target endothelial cells crucial to the blood-brain barrier, causing blood vessel thinning and leaks between the tight-junctions of cells13. Once leakage occurs, immune cells such as macrophages attempt to repair the damage and initiate inflammation pathways. Researchers from this study found that in areas were endothelial cells were damaged, 300 genes showed decreased expression, while genes associated with oxidative stress were increased. Numerous other studies have linked oxidative stress to the brain-fog and fatigue experienced by people with long-COVID9-12.

In a lab at La Trobe University in Australia, a team of researchers led by Dr Nick Reynolds have just linked the pathophysiology of long-COVID to neurodegenerative processes previously only observed in Alzheimer’s disease, with deposits of amyloid-like plaques identified in brain tissues14.

To cut a long story short, these amyloid plaques are very toxic to the brain cells, and we hypothesise that aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19 that many of us call brain fog.
Dr Nick Reynolds, Nicholas Hoogenraad Fellow at La Trobe University.

If this is confirmed in future studies, Reynolds believes drugs developed to combat Alzheimer’s and Parkinson’s could be repurposed to revolutionise treatment for the debilitating neurological symptoms of long-COVID.

What is interesting about this novel long-COVID research is that it mirrors research that has been published about CFS/ME for years. For example, a similar pattern of grey and white matter loss has been observed in the brains of people with CFS/ME15,16, while neuroinflammation mediated by oxidative stress has also been well documented17-21. A recently published case study also found amyloid-like plaque build-up in a patient with CFS and notes that further investigations into the role of CNS disease in CFS/ME is warranted22.

The similarities between these two conditions are becoming undeniable, affording validation and hope to millions of people suffering from the debilitating symptoms of chronic fatigue and cognitive impairment. As scientists continue to decipher the parallels between long-COVID and CFS/ME, the findings have potential to help both groups of patients.


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