ME/CFS, Long Covid & the Mind-Body Approach: The Scientific Basis

Dr. Martina Melzer, published: 3/21/26

Text translated from German with DeepL

ME/CFS is considered an incurable disease. This assumption is widely held by scientists, reputable media outlets, and patients. The same assumption applies when a person has “Long Covid” and meets the criteria for ME/CFS. 

Nevertheless, many people recover from ME/CFS and Long Covid (with ME/CFS). This is demonstrated, for example, by podcasts where they share their stories. These include “The Raelan Agle Podcast” (English), “Superhelden ohne Cape” (German), “The Story Behind the Symptoms” (English), “Ich werde gesund” (German, my podcast), “Fasynation” (German), and “The Cure for Chronic Pain” (English).

The assumption that the condition is incurable cannot therefore be correct. Scientists also share this view. Miller et al. write in an opinion piece (1): The unproven portrayal of a disease for which there is neither a cure nor improvement or recovery can be harmful and is false. And further: A new perspective on the disease, in conjunction with specialist rehabilitation, can support the recovery of people with severe ME/CFS.

The Oslo Chronic Fatigue Consortium, an international group of scientists dedicated to researching chronic fatigue, states (2): We challenge the prevailing view that chronic fatigue syndromes, including post-COVID conditions, are incurable diseases. Instead, we propose an alternative perspective based on scientific evidence that offers patients more hope.

In addition to the purely biomedical explanation for these conditions, another has gained traction. It stems from neuroscience and psychosomatics. According to this model, certain biological, psychological, and social factors increase the likelihood of developing Long COVID and ME/CFS (biopsychosocial model of illness). 

For example, a study by Fazekas et al. concludes that a higher level of pre-existing chronic stress increases the risk of developing a prolonged symptomatic course of COVID-19 (3). Heim et al. write: Our findings suggest that childhood trauma is an important risk factor for CFS. Across various types of trauma, childhood trauma was associated with a 3- to 8-fold increased risk of CFS (4). Muller et al. conclude in a review: The four most common factors triggering ME/CFS were: immunological factors (297 studies), psychological factors (243), infections (198), and neuroendocrine factors (198) (5). 

Saunders et al. note (8): Despite intensive research in this field, no clear pathogenesis has yet been identified that could explain the full spectrum of Long COVID symptoms. Two studies have shown that, in many cases, patients’ symptoms persist beyond the point at which they could be adequately explained by pathophysiological observations. Long COVID could be described as a physically experienced condition in which heterogeneous biological, psychological (experience-related), and social (or environmental) factors are intricately intertwined in complex interactions.

The reason why symptoms persist after such triggering factors could be the way the brain works. The brain constantly makes predictions in order to process information from the external world and the body. This is called predictive processing or predictive coding. 

Löwe et al. describe this in a review article on persistent physical symptoms such as pain, fatigue, dizziness, palpitations, constipation, weakness, etc. (6): 

Although biomedical factors are generally—though not always—central to the onset of short-term symptoms, psychological factors (such as the patient’s beliefs or expectations) and social factors appear to play a greater role in the long-term persistence of somatic symptoms. 

Common biomedical factors such as persistent inflammation and dysregulation of the immune, autonomic, metabolic, and microbiome systems, as well as genetic and epigenetic factors, can lead to the persistence or exacerbation of somatic symptoms. Cognitive-perceptual and emotional processes considered to be maintaining and exacerbating factors in the development of persistent physical symptoms across various conditions include selective attention and heightened awareness of bodily sensations, catastrophic interpretations, dysfunctional health behaviors, and somatosensory amplification. Alexithymia, a deficit in the perception and regulation of emotions, is considered an affective risk factor. At the cognitive-behavioral level, learning processes and avoidance behaviors such as physical inactivity and resulting deconditioning also play a role in the maintenance and amplification of somatic symptoms.

There is growing evidence that symptoms are imprecise representations of bodily states. This imprecision can lead to an over- or underestimation of the activity of disease processes. The process of predictive coding is of central importance for a contemporary neuroscientific explanation of symptoms.

In the case of persistent physical symptoms, the findings suggest that prior assumptions based on implicitly learned experiences with symptoms or explicit beliefs have a dominant influence, while the effect of ascending signals (note: from the body) is attenuated. Thus, predictive coding models explain how somatic symptoms can persist over the long term even in the absence of sensory stimuli, provided that strong preconceptions are present.

I quote another scientific paper by Joffe and Elliott (7) on Long Covid:

In the Bayesian predictive coding model, several factors influence the perception of symptoms. First, the nature of the sensory stimuli. If the stimuli are less intense, more systemic and widespread, and lack clear boundaries between “on” and “off” (e.g., in fatigue or malaise), or if there is interoceptive dysfunction with a low signal-to-noise ratio (e.g., in chronic stress with activation of the cytokine and stress axes), this reduces the precision of sensory stimuli, giving prior expectations more room to determine perception. Conversely, when stimuli are associated with strong cues (e.g., previous symptoms of a viral infection or panic attacks), these cues can later activate strong prior expectations that override incoming sensory interference signals.

Second: the focus of attention. One can think of attention as regulating the balance between the “weights” of sensory stimuli and prior expectations. Third: Genetic influences. For example, women appear to be more sensitive to contextual cues that influence their prior expectations. 

Fourth: Trait anxiety, particularly in the face of an anticipated threat and negative emotions (involving harm avoidance, catastrophizing, and fear). Chronic worry and stress can trigger a vicious cycle, with increased threat and salience detection (e.g., through the activation of preconceptions that predict a threat and are categorically precise) and lead to active inference (e.g., activation of the autonomic nervous system, the endocrine system, and the immune system to generate inaccurate inputs that correspond to the previous predictions), which reinforces the previous belief. Fifth: Top-down presuppositions and expectations. Self-fulfilling health-related expectations can lead to pathologically precise presuppositions.

All these factors can lead to three erroneous conclusions being drawn during hierarchical Bayesian processing in the brain. First: “The autonomous emergence of a perception or belief that, following top-down modulation of synaptic weighting by attention, is held with unjustified certainty (precision).” Second: This perception “is mistakenly interpreted as a symptom to explain why its content was not predicted by the [superordinate] source of attentional modulation.” Third: Active inference, in which interactions lead to sensory inputs that correspond to the predictions and reinforce the precision of abnormal prior expectations.

The Oslo Chronic Fatigue Network writes (2): 

After 40 years of research on CFS/ME, neither a specific biological defect or pathology nor a specific biomarker has been identified. Although numerous pathophysiological abnormalities have been reported, these remain nonspecific findings. Similar abnormalities have also been observed in patients with other conditions, including chronic pain and fibromyalgia, as well as in conditions commonly labeled as “psychological.” We therefore believe it is time to explore alternative perspectives that incorporate psychological, social, and biological factors. 

This new perspective views the symptoms of these states of exhaustion as real. Like all perceptions, these symptoms arise from the synchronized activity of complex neural networks in the brain. While this activity can be triggered by signals originating in body tissues, it can also occur without such signals. 

In response to perceived threats to our well-being, our brain networks generate alarm signals in the form of symptoms such as fatigue and pain to warn us. These alarms can be viewed as critical processes that have been selected through evolution to protect us. More specifically, pain signals tissue damage, and fatigue signals an imbalance between required effort, expected reward, and available resources, yet they are also regulated and influenced by context.

These perceived threats to our safety can trigger a stress response involving automated physical defense mechanisms, consisting of interconnected immunological, hormonal, cognitive, and behavioral adaptations. This response is initially temporary and adaptive, but it can become persistent and maladaptive, chronically impairing sleep and cognitive functions. A high degree of neuroplasticity in this alarm system carries the risk of associative learning, whereby the alarms are reactivated by harmless stimuli (through classical conditioning).

There may thus be a kind of communication breakdown between the brain and the body, sustained by emotional, cognitive, and behavioral factors. These, in turn, activate biological factors.

From my own experience, I can say this: When I discovered Raelan Agle’s YouTube channel a few years ago where she shared her own recovery story and, since then, hundreds of others a whole new world opened up to me. I found hope. It was possible that my condition could improve or that I might even recover.

Early studies confirm my personal experience and also show that recovery is possible.

Bakken et al. surveyed 14 people who had very severe ME/CFS and described themselves as fully recovered (9). The result: There was a clear turning point that these people identified. “The participants underwent a profound narrative shift, a change in their mindset, and subsequent long-term work toward actively pursuing their own healing. Their narrative understanding of being helpless victims of an illness was replaced by a more complex view of causality and illness, and a new sense of self-efficacy developed.”

Krabbe et al. spoke with 13 young women who had recovered from severe ME/CFS (10): “Recovery from ME/CFS proves to be an interpersonal, context-dependent, fragile, and nonlinear process of returning to oneself, based on a gradually deepening body-based self-awareness. The illness slowly recedes into the background, and the prospect of a healthier future begins to emerge. It is crucial to note that the recovery process typically takes years, and setbacks are inevitable. Illustrating this temporal dimension can help those affected by highlighting the value of patience, a willingness to learn, and the determination never to give up.”

The Oslo Chronic Fatigue Network adds (2): “We believe that the voice of patients is important and that this voice must also include those who are doing better or have recovered from the illness, not just those who remain ill. Those who are doing better or have recovered through cognitive, behavioral, and stress-reducing strategies can offer unique insights into both the experience of the illness and the paths out of it.”

Again and again, however, I find that I or the people who share their stories with me are attacked by those who are ill. And this is also addressed in studies. For example, I recognize myself in this man who speaks about his experiences in this regard in Bakken et al.: “Sharing his story comes at a price. You can get caught in the crossfire of heated public and scientific debates about ME/CFS. People doubt that you had ‘real’ ME/CFS, that you’ve truly recovered.”

The numerous recovery stories published online show that every path to recovery is highly individual. Nevertheless, many people repeatedly report that the so-called “mind-body approach,” “nervous system approach,” or “neuroplastic approach” has helped them. This is intended to illustrate that processes in the body and mind, in the autonomic nervous system, and in the brain (through neuroplasticity) have played an important role in the illness and recovery.

Currently, there are still very few studies that have examined this approach as a potential therapeutic option. Hopefully, this will change.

Some excerpts of therapeutic approaches from scientific publications:

• Changing dysfunctional expectations regarding symptoms and treatment, managing illness-related fears, altering catastrophic interpretations, symptom-focusing, and somatosensory amplification, reducing symptom-related impairment, providing a biopsychosocial explanatory model, treating comorbid depressive disorders, anxiety disorders, and sleep disorders, improving emotion regulation skills, and addressing early childhood trauma (6).

• Reducing modifiable risk factors for functional syndromes: This would entail a reduction in health anxiety (including worries and catastrophic thinking), depression, anxiety (including perceived threats and excessively negative expectations), negative media coverage (including by medical “experts”), social isolation, and physical inactivity. Reduction of modifiable maintaining factors for functional syndromes: This would involve reducing physical inactivity, social isolation, health anxiety (including unhelpful cognitions and fears), depression, social reinforcement, as well as the contagion effect of (sometimes dramatic) exaggerations in conventional and social media, and delayed or missed diagnosis (7). 

• Psychophysiological Symptom Relief Therapy (PSRT) can effectively reduce symptom burden in patients with PASC (post-acute sequelae of coronavirus disease) who show no signs of organ damage. The goal of PSRT is to address underlying stressors and psychological factors in order to mitigate conditioned symptom responses and anxiety-avoidant behaviors triggered by these factors (11). 

• Short-term rehabilitation program for post-COVID-19 sequelae: The intervention was based on the premise that every stressful event (both psychological and biological) requires an adaptive response, which can entail physical symptoms. Normally, the adaptive response is brief and self-limiting. However, a persistent reaction can have adverse effects and lead to a variety of physical symptoms. Cognitive factors, such as unconscious expectations, are key determinants of the extent and duration of the adaptive reaction. Of particular importance are stimulus expectations influenced by classical conditioning and response expectations arising from operant conditioning; changing these expectations is thus the goal of the intervention. In this randomized clinical trial, the program proved to be an effective and safe approach for patients with post-COVID-19 sequelae (12).

• Mind-Body Reprogramming Therapy for Long COVID: The MBRT treatment program is designed for patients whose functional capacity is significantly impaired due to Long COVID. It consists of two components, both of which are based on three theoretical pillars. The first is an educational module that clearly explains patients’ symptoms. The second comprises practical techniques and exercises aimed at stress regulation and the brain’s processing of symptom warning signals. The three theoretical pillars on which the intervention is based are 1) predictive processing, 2) classical and operant conditioning, and 3) Relational Frame Theory. MBRT helps patients recalibrate and deactivate maladaptive “alarm” circuits in the brain, leading to a reduction in symptoms—and in some cases, complete recovery. This hypothesis is currently being evaluated in an ongoing randomized controlled trial

• A systematic review of mind-body therapies for ME/CFS: Interventions included mindfulness-based stress reduction, mindfulness-based cognitive therapy, relaxation techniques, qigong, cognitive-behavioral stress management, acceptance and commitment therapy, and isometric yoga. The most commonly measured outcomes were the severity of fatigue, anxiety/depression, and quality of life. Nine and eight studies, respectively, showed improvements in the severity of fatigue and in anxiety and depression symptoms, and three studies concluded that mindfulness-based interventions improved quality of life (14).

Note: Even though some parts may be a bit difficult to understand, I have deliberately retained the original wording from the cited sources for the most part. This text is intended to demonstrate that the approach has a scientific basis.

My conflict of interest: 

I support people on their journey to recovery from Long Covid and ME/CFS through coaching sessions and courses, using the approach described above.

(1) Miller A, Symington F, Garner P, Pedersen M. Patients with severe ME/CFS need hope and expert multidisciplinary care BMJ 2025; 389 :r977 doi:10.1136/bmj.r977

(2) Oslo Chronic Fatigue Consortium; Alme TN, Andreasson A, Asprusten TT, Bakken AK, Beadsworth MB, Boye B, Brodal PA, Brodwall EM, Brurberg KG, Bugge I, Chalder T, Due R, Eriksen HR, Fink PK, Flottorp SA, Fors EA, Jensen BF, Fundingsrud HP, Garner P, Havdal LB, Helgeland H, Jacobsen HB, Johnson GE, Jonsjö M, Knoop H, Landmark L, Launes G, Lekander M, Linnros H, Lindsäter E, Liira H, Linnestad L, Loge JH, Lyby PS, Malik S, Malt UF, Moe T, Norlin AK, Pedersen M, Pignatiello SE, Rask CU, Reme SE, Roksund G, Sainio M, Sharpe M, Thorkildsen RF, van Roy B, Vandvik PO, Vogt H, Wyller HB, Wyller VBB. Chronic fatigue syndromes: real illnesses that people can recover from. Scand J Prim Health Care. 2023 Dec;41(4):372-376. doi: 10.1080/02813432.2023.2235609. Epub 2023 Nov 29. PMID: 37740918; PMCID: PMC11001335 

(3) Christian Fazekas, Nandu Goswami, Franziska Matzer, Alexander Avian, Julia Lodron, Marc Rijksen, Barbara Hanfstingl, Voyko Kavcic, Andrea Groselj-Strele, Harald Sourij, Harald H. Kessler, Evelyn Stelzl, Clarissa Daniela Voegel, Tina Maria Binz, Karin Schmid-Zalaudek, Alexander Wittmann, Stefan Pilz; Perceived Chronic Stress prior to SARS-CoV-2 Infection Predicts Ongoing Symptomatic COVID-19: A Prospective Cohort Study. Psychother Psychosom 9 February 2026; 95 (1): 76–87. https://doi.org/10.1159/000547858 

(4) Heim C, Wagner D, Maloney E, et al. Early Adverse Experience and Risk for Chronic Fatigue Syndrome: Results From a Population-Based Study. Arch Gen Psychiatry. 2006;63(11):1258–1266. doi:10.1001/archpsyc.63.11.1258

(5) Muller AE, Tveito K, Bakken IJ, Flottorp SA, Mjaaland S, Larun L. Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched. J Transl Med. 2020 Dec 14;18(1):484. doi: 10.1186/s12967-020-02665-6. PMID: 33317576; PMCID: PMC7734915

(6) Löwe B, Toussaint A, Rosmalen J et al. Persistent physical symptoms: definition, genesis, and management. The Lancet, 403, 2649-2662


(7) Joffe AR, Elliott A. Long COVID as a functional somatic symptom disorder caused by abnormally precise prior expectations during Bayesian perceptual processing: A new hypothesis and implications for pandemic response. SAGE Open Med. 2023 Aug 24;11:20503121231194400. doi: 10.1177/20503121231194400. PMID: 37655303; PMCID: PMC10467233 

(8) Saunders C, Sperling S, Bendstrup E. A new paradigm is needed to explain long COVID. The Lancet Respiratory Medicine, 2023; 11, e12-e13


(9) Bakken, A. K., Mengshoel, A. M., Synnes, O., & Strand, E. B. (2023). Acquiring a new understanding of illness and agency: a narrative study of recovering from chronic fatigue syndrome. International Journal of Qualitative Studies on Health and Well-Being, 18(1). https://doi.org/10.1080/17482631.2023.2223420 

(10) Krabbe, S. H., Groven, K. S., Schrøder Bjorbækmo, W., Sveen, U., & Mengshoel, A. M. (2023). The fragile process of Homecoming - Young women in recovery from severe ME/CFS. International Journal of Qualitative Studies on Health and Well-Being, 18(1). https://doi.org/10.1080/17482631.2022.2146244 

(11) Donnino M, Howard P, Mehta S, Silverman J, Cabrera MJ, Yamin JB, Balaji L, Berg KM, Heydrick S, Edwards R, Grossestreuer AV. Psychophysiologic Symptom Relief Therapy (PSRT) for Post-acute Sequelae of COVID-19. Mayo Clin Proc Innov Qual Outcomes. 2023 May 19;7(4):337–48. doi: 10.1016/j.mayocpiqo.2023.05.002. Epub ahead of print. PMID: 37361483; PMCID: PMC10196153 

(12) Nerli TF, Selvakumar J, Cvejic E, et al. Brief Outpatient Rehabilitation Program for Post–COVID-19 Condition: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(12):e2450744. doi:10.1001/jamanetworkopen.2024.50744 

(13) Henrik Børsting Jacobsen, Silje Endresen Reme. Mind-Body Reprogramming Therapy for long COVID: Theory and practice. Authorea. July 09, 2025 

(14) Khanpour Ardestani S, Karkhaneh M, Stein E, Punja S, Junqueira DR, Kuzmyn T, Pearson M, Smith L, Olson K, Vohra S. Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Medicina (Kaunas). 2021 Jun 24;57(7):652. doi: 10.3390/medicina57070652. PMID: 34202826; PMCID: PMC8305555