Infectious Diseases

New evidence affirms link between long COVID and chronic fatigue syndrome

A study found around half of the long COVID patients examined fit the diagnostic criteria for chronic fatigue syndrome
A study found around half of the long COVID patients examined fit the diagnostic criteria for chronic fatigue syndrome

A new study published in Nature Communications has added to the growing body of evidence reporting similarities between long COVID and chronic fatigue syndrome (ME/CFS). The research found around half of the long COVID patients studied fit the diagnostic criteria for ME/CFS.

Chronic fatigue syndrome is also known as myalgic encephalomyelitis (ME), and often referred to under the umbrella term ME/CFS. Over the last few years researchers have slowly begun to better understand this disease, and one hypothesis to emerge suggests it can be triggered by an acute viral infection.

A number of different pathogens are suspected to trigger ME/CFS, from the Epstein-Barr virus to dengue viruses. And some researchers speculate up to 75% of ME/CFS cases can be directly traced to a viral infection.

So when patients in 2020 started to experience persistent fatigue-like illness following acute SARS-CoV-2 infections plenty of researchers began joining the dots. Long COVID, now dubbed by many clinicians as PASC (Post-Acute Sequelae of SARS-CoV-2 infection), is a condition with a diverse set of symptoms, but many patients report features similar to ME/CFS, such as brain fog and reduced exercise capacity.

Carmen Scheibenbogen, an ME/CFS researcher at Charité - Universitätsmedizin Berlin, has spent the better part of the last two years investigating the overlap between the two post-viral conditions. In a new study Scheibenbogen and colleagues have confirmed COVID-19 can trigger ME/CFS in some people.

"Providing the scientific evidence to confirm these assumptions, however, is anything but a trivial task," said Scheibenbogen. "This is partly due to the paucity of research into ME/CFS and the fact that there are no universally accepted diagnostic criteria. Thanks to an extremely thorough diagnostic process and a comprehensive comparison with patients who developed ME/CFS following non-COVID-related infections, we have now been able to show that COVID-19 can trigger ME/CFS."

This study is the first published data from an ongoing project tracking post-viral fatigue in COVID-19 patients. The research focused on 42 young participants, all experiencing persistent moderate to severe fatigue and exertion intolerance at least six months after an acute bout with COVID-19.

The majority of the cohort only suffered from a mild initial case of COVID-19. Just three were admitted to hospital during their acute infection, and all participants were unvaccinated.

This PASC cohort was compared to a control group consisting of age- and sex-matched ME/CFS patients known to have developed their disease following a short period of illness from a non-COVID infection.

Around half of the post-COVID cohort fit the diagnostic criteria for ME/CFS. The main distinguishing feature that separated the post-COVID ME/CFS cohort was the duration of exhaustion following exertion or exercise. In ME/CFS patients, and post-COVID patients fitting the diagnostic criteria for ME/CFS, post-exertional malaise lasted well over 24 hours.

Perhaps the most interesting findings in the study were the differences between the post-COVID ME/CFS subjects and the control ME/CFS patients. A measurement of hand grip strength is often used to quantify muscle fatigue in ME/CFS, and similar weaknesses were detected between the COVID and non-COVID ME/CFS patients on this measure. But curiously they correlated with very different inflammatory biomarkers.

"We furthermore found that [post-COVID] individuals with milder exertional intolerance had reduced hand grip strength if they had elevated levels of the cytokine interleukin 8,” noted Scheibenbogen. “In the ME/CFS group, however, hand grip strength was correlated with the hormone NT-proBNP, which can be released by muscle cells when oxygen supply is insufficient. This suggests that, in these individuals, muscle weakness may be caused by an impaired blood supply."

So what does all this mean? Unfortunately the frustrating answer is, it’s complicated. Maybe more complicated than many researchers previously suspected.

These new findings indicate long COVID, or PASC, is an incredibly heterogeneous chronic disease. In some patients it may manifest in conditions that resemble ME/CFS, but for others long COVID can included a number of novel neurological, vascular or cardiovascular symptoms.

The new findings also imply ME/CFS is potentially a much more diverse disease than suspected. The study does speculate post-viral fatigue could manifest in different ways depending on the pathogen triggering the condition. So maybe Epstein-Barr-triggered ME/CFS is pathologically different to SARS-CoV-2-triggered ME/CFS?

Better understanding the specificity of these kinds of post-viral fatigue syndromes will help researchers develop future treatments. But Scheibenbogen does stress there are currently few treatments to help patients with these conditions, so trying to avoid viral infections is probably the best course of action at this point in time.

"Our data also provide further evidence that ME/CFS is not a psychosomatic disorder but a severe physical disease which can be measured and diagnosed using objective methods," Scheibenbogen added. "Unfortunately, current treatments for ME/CFS are purely symptomatic in nature. I would therefore urge even young people to protect themselves against SARS-CoV-2 by getting vaccinated and wearing an FFP2 mask."

The new study was published in Nature Communications.

Source: Charité - Universitätsmedizin Berlin

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1 comment
Kerry Newnham
ME/CFS was recognised by sympathetic doctors, and asserted by patients themselves, as a post-viral syndrome. It is not an emerging hypothesis it just wasn't Acknowledged as such by the medical establishment, who chose to see it as a mysterious disorder best understood as a “biopsychosocial” condition. This ignoring of both patient testimony and the expertise from the ME/CFS field, has had a devastating impact on recognition and appropriate research and funding.

Just as with long covid, “most“ pwME were high functioning or fully well before a virus Laid them low and they never properly recovered From it. Just as with LC, to many ME/CFS patients the sudden loss of health was easily attributable to a virus. There are also a minority who report a gradual or non viral ME/CFS onset.