Interesting Research | ME|FM Society of BC

Interesting Research on ME and Long-COVID

A few highlights of current and upcoming research

Neither ME/CFS nor Long-COVID are well understood.

The root causes are not known, there are no widely-accepted biomarkers or tests to help with diagnosis, and there are no cures or universally effective treatments that work for everyone. However, there is good research on symptom management that can improve quality of life for many people.

Especially since attention has been drawn to post-viral and fatigue illnesses since COVID-19, there is a lot of good and interesting research coming out for each illness individually (ME/CFS and Long-COVID) as well as interesting information about how these two illnesses overlap and interact.

On this page, we give you:

a link to an excellent weekly research summary on ME/CFS and Long-COVID (by The ME Association)
some links that will perform current searches in PubMed (an online database of peer-reviewed references for biomedical topics)
some summaries and links to a few interesting articles on:
- symptoms, biomarkers and diagnosis
- potential treatments (general and symptom-specific).

Note: This page was last updated in August, 2024.

A couple of notes:

The links here are primarily detailed, peer-reviewed, scientific articles and may be a challenge to digest.
- We have more “usable” tools and information for understanding and managing your illness in previous modules on pacing, treatments and other topics.

Most research on ME/CFS and especially Long-COVID is new, preliminary, in smaller studies, and/or in need of further research.
- If you read something interesting here, continue to follow the research to understand if the preliminary findings end up being supported and confirmed in the longer-term.

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Some good links and searches for ME/CFS and Long-COVID research

The ME Association maintains a comprehensive index of published research on ME/CFS and Long-CoVID that is free to use and updated weekly here. For research on treatments, scroll down to the section titled “Management” (sections are listed alphabetically).

To search PubMed for current articles on Treatments for ME/CFS and Long-COVID, click here.

To search PubMed for current articles on features, causes and biomarkers of ME/CFS and Long-COVID, click here.

To search PubMed for general articles on ME/CFS and Long-COVID, click here.

Symptoms, Biomarkers and Diagnosis

Symptoms and biological abnormalities in ME/CFS and Long-COVID

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This literature review summarizes how both illnesses show persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias, orthostatic intolerance and other key symptoms. Both illnesses also share similar underlying pathophysiologies, including abnormalities in the central and autonomic nervous systems, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism, and redox balance.

Some of these may lead in the near future to helpful tests or more “objective” diagnostic criteria (current diagnosis is done primarily based on self-reported symptoms and elimination of other illnesses).

Symptom similarities between ME/CFS and Long-COVID

Several articles discuss the significant overlap in symptoms, including the key symptoms of PEM (post-exertional malaise), fatigue, cognitive issues (brain fog), sleep disturbances and pain. One article notes that at least 20 of the 25 main symptoms of ME/CFS are shared with Long-COVID patients. This is promising news for ME patients as Long-COVID research continues.

Possible differences in triggers and symptoms of PEM between ME/CFS and Long-COVID patients

This article notes some possible differences in how PEM (or a worsening of symptoms after physical, mental or emotional exertion) is triggered or experienced between people with ME/CFS and people with Long-COVID. But it notes that these differences may be due more to the newness of Long-COVID and differences in understanding how to manage, methods of recovering from, and approaches to preventing exertional intolerance. More research on this is required to understand if there may or may not be any helpful differences in advice to patients for successful Pacing.

Some specific potential root issues and dysfunctions of these illnesses

Several articles discuss current research around dysfunctions and biomarkers of ME/CFS and Long-COVID. A few examples include:

Endothelial dysfunction and biomarkers

Some general Long-COVID findings, mechanisms and recommendations. This article discusses both long-term organ and other damage from COVID, as well as the Long-COVID that has overlapping diagnostic criteria with ME/CFS.

Reduction in cerebral blood-flow and related orthostatic symptoms

Neurological complications and autonomic nervous system dysfunction. This last article also looks at a genetic component.

Metabolomic and immune differences (Long-COVID patients that meet diagnostic criteria of ME/CFS)

Viral persistence and reactivation (and neuroinflammation, blood clotting abnormalities, and autoimmunity) in Long-COVID

Mitochondrial dysfunction (which can cause muscle weakness and energy, neurological, organ and metabolic issues) – possible explanations

Sources of inflammation and autoimmunity in Long-COVID

Symptom severity and biomarkers

Potential neurophysiological biomarkers for ME/CFS and Long-COVID

Shared mechanisms - ME/CFS and Long-COVID pathologies

Oxidative stress (an imbalance between free radicals and antioxidants in the body, leading to cell and tissue damage) in ME/CFS and Long-COVID

Hyperactivated Platelets and Microclots (blood markers) (Long-COVID and ME/CFS). On origins and treatment implications of amyloid fibrin microclots in Long-COVID.

Sleep and circadian rhythm disruption in ME/CFS and Long-COVID. Associations with cardiovascular risk.

Potential genetic risk factors for severe and fatigue-dominant Long-COVID and ME/CFS

Microbiome (gut health) in ME/CFS and Long-COVID (article 1, article 2)

Areas of Research into Potential Treatments

General overviews and multi-symptom treatment research

An overview of ongoing efforts to discover new medicines for ME/CFS (2021)

Low Dose Naltrexone treatment based on the science of the role of the ion channel TRPM3. Another article on potential treatment based on restoration of TRPM3 ion channel activity.

Melatonin as a possible treatment for memory loss, brain fog, inflammation and pain, as well as the better-known uses for improving sleep

Ion channel inhibition and immunomodulation as potential treatments

This article (in a table halfway down the page) has an excellent summary of the types of treatments
that may be used to handle the various key symptoms of these illnesses, such as post exertional malaise,
fatigue, sleep issues, cognitive dysfunction, orthostatic intolerance, dizziness, muscle or joint pain,
neuropathy, sensory amplification, and gastrointestinal symptoms. It highlights that, generally,
treatments are addressing specific symptoms and that there is need for more research.

Note: Experiment carefully and find what works best for you.

For fatigue

(including mitochondrial dysfunction and pain)

Oxaloacetate treatment for fatigue in ME/CFS and Long-COVID

Coenzyme Q10 for fatigue and pain

For brain fog

Luteolin as potential treatment

For exercise intolerance

Research on how WASF3 may mediate exercise intolerance in ME/CFS. WASF3 (Wiskott–Aldrich syndrome protein family member 3) is a gene that encodes a protein involved in cell shape, movement, and function.

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Cognitive, psychological, mind-body and similar practices

Following a general online search, a review of the articles on PubMed, and a quick chat with a local physician, it seems that there are few current, well-designed, peer-reviewed articles on the use of most of these types of practices for ME/CFS or Long-COVID.

The notes below (and cautions to the right) may help you navigate the confusing conversations on these topics in current medical, online, and social media settings.

Caution: There are groups (including ones looking to charge money for their programs) that are claiming psychological or brain treatments (like Cognitive behavioural therapy or hypnosis) are cures or have strong positive improvement impacts on ME/CFS and Long-COVID.

Current research tends to agree that, while some people do find moderate benefit in some of these treatments for living with these difficult chronic illnesses, they are not cures and often lead to little or no improvements, and sometimes harm, in many patients.

Be cautious if someone is trying to sell you an expensive “program” based on these types of treatments.

CBT, other psychological therapies

In the past, ME/CFS had been treated largely as a psychosocial or “all-in the head” condition. People were told that they were burned out, lazy, fearful of exercise, deconditioned, anxious and just needed to exercise, get better sleep, and allow themselves to get back to normal. Some doctors still think this way.

Based on this incorrect perspective, CBT or cognitive behavioural therapy was often recommended in order to reset the patients’ thinking and “get them back to normal.” There were a couple of initial studies that suggested that this approach did, in fact, work. But, more recently, several studies (as well as overwhelming feedback from the patient community) have debunked those studies, noting that they were incomplete, poorly designed, had too-short-term follow-up and included many people who did not meet the diagnostic criteria for ME/CFS.

Now, the science and major health authorities such as the CDC and NIH recognize that CBT (and its common bedfellow GET or Graded Exercise Therapy) touted as a cure for ME/CFS and Long-COVID is not only unhelpful, but usually harmful.

Science has shown incontrovertibly that ME/CFS and Long-COVID are real, physiological illnesses, with real, measurable physiological symptoms, effects and biomarkers.

The world-leading NICE guidelines on ME/CFS state that CBT is not a treatment or cure for ME/CFS. The guidelines also note that CBT can consume precious energy, misinform patients, and potentially contribute to harm.

Psychological therapy may offer some support for some patients for the challenges of living with a debilitating illness, but people with ME/CFS and Long-COVID do not have “abnormal beliefs and behaviours” as the underlying issue or cause of their conditions. Care should be focused on energy limits and symptom management, which may include co-morbidities such as anxiety or depression, that may improve for some people with medication and/or psychological therapy.

Meditation and hypnosis

While it is important to note that meditation, hypnosis and other neuroplasticity and psychological treatments/practices are not cures for ME/CFS or Long-COVID, there is some anecdotal evidence and a few studies that suggest that some of these exercises may improve sleep, help moderate nervous system over-activation, and (possibly as a side effect of the first two results), potentially reduce fatigue and cognitive issues.

Many argue that the main benefits are likely general relaxation, mindfulness, and better attention to one’s symptoms and energy levels. These potential benefits should not be discounted if they work for you.

Simply be clear that none of these types of practices are cures and be cautious in your optimism around how much these practices will be able to improve your condition.

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“I have had moderate success with using "medical" interventions to address symptoms ....ie LDN, valcyclovir... I have had equally as impactful alleviation of symptoms ... with complementary modalities: acupuncture, chiropractic, meditation, and hypnosis. They are all very different and impact me differently.”

- ME/CFS patient in Langley BC

“My doctor keeps pushing meditation apps on me. But I hate those apps. It is exhausting to use them and they don’t help me. If it causes a calming or relaxation for other people, that’s great. But I have different ways to rest and Pace that work for me. Stop telling me I have to meditate! And stop not-so-subtly acting like if I don’t use the apps you tell me to that I am not taking my own care seriously. I think my doctors secretly still think this is all in my head.”

- Long-COVID, ME patient in Surrey BC

A few links

An extensive literature review that concludes that “graded exercise therapy (GET) is harmful and should not be used, and that cognitive behavioural therapy (CBT) is only an adjunctive and not a curative treatment.” Includes links to other articles on GET and CBT from 2009 through 2024.

Here is one article on the potential impacts of mindfulness meditation.

A 2022 literature review that notes: "Clinical research has demonstrated a decrease of pain perception" using hypnosis in people with chronic pain.

The NICE guidelines from the NIH in England gives solid, science-based recommendations for managing ME/CFS (also applicable to Long-COVID that meets the ME diagnostic criteria) and discusses some of these issues.