Evidence browser

E3 PreliminaryMechanismPEM not requiredMechanistic

Understanding myalgic encephalomyelitis.

Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie·Science (New York, N.Y.)·2022

This article examines myalgic encephalomyelitis (ME/CFS), a serious illness that causes extreme tiredness, pain, and other symptoms that get worse after activity. The researchers note that ME/CFS and Long COVID (a condition affecting some people after COVID-19) share many similar features. Understanding these overlaps may help doctors better recognize and treat both conditions.

Metabolomics study of the effect of Danggui Buxue Tang on rats with chronic fatigue syndrome.

Miao, Xiaoyao, Li, Shuo, Xiao, Bingkun et al.·Biomedical chromatography : BMC·2022

Researchers tested whether a traditional Chinese medicine formula called Danggui Buxue Tang (DBT) could help rats with chronic fatigue syndrome caused by stress and food restriction. After 4 weeks of treatment, rats given DBT showed better energy levels, reduced fatigue markers in their blood, and improved physical performance compared to untreated rats with CFS.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Recovering from chronic fatigue syndrome as an intra-active process.

Groven, Karen Synne, Dahl-Michelsen, Tone·Health care for women international·2022

This study examined the story of one woman who recovered from ME/CFS to understand how healing from this illness happens. Instead of debating whether ME/CFS is 'purely physical' or 'purely psychological,' the researchers looked at how many different factors—including both biological and non-biological elements—worked together in her recovery. The study suggests that recovery involves the interaction of many different things in a person's life, not just one single cause.

E3 PreliminaryCohortPEM unclearCase-Control

Stellate Ganglion Block for Long COVID Symptom Management: A Case Report.

Khan, Mashfee H, Kirkpatrick, Kennedy P, Deng, Yi et al.·Cureus·2022

This study describes one patient with long COVID who received a stellate ganglion block (SGB)—an injection that calms an overactive nervous system. The treatment helped reduce their fatigue, post-exertional malaise (worsening after activity), shortness of breath, and stomach problems. Because the nervous system controls many body functions, blocking specific nerve signals may help relieve symptoms driven by this dysregulation.

Post-Exertional Malaise

Understanding Long Covid: Nosology, social attitudes and stigma.

Byrne, Eleanor Alexandra·Brain, behavior, and immunity·2022

This article discusses how Long Covid patients face stigma and discrimination similar to what ME/CFS patients have experienced for decades. The author argues that refusing to acknowledge these similarities actually reinforces stigma against both conditions. The piece emphasizes that these attitudes can harm patients by limiting how they're able to describe and understand their own illness experiences.

Energy MetabolismPost-Exertional Malaise

Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach.

Wirth, Klaus J, Scheibenbogen, Carmen·Medicina (Kaunas, Lithuania)·2022

Many people with post-COVID syndrome experience shortness of breath and chest pain, even though their lungs and heart are typically healthy. This study proposes that the problem may stem from overbreathing (hyperventilation) during exercise, combined with problems in how the body regulates breathing and uses energy in muscles. The authors suggest that overbreathing creates a harmful cascade inside cells—disrupting sodium and calcium balance—which worsens fatigue and breathing difficulties. Preventing overbreathing might be a way to help these patients recover.

Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study.

Jahanbani, Fereshteh, Maynard, Rajan D, Sing, Justin Cyril et al.·PloS one·2022

Researchers used a powerful microscope to examine immune cells from people with ME/CFS and found several abnormalities. They observed that immune cells from ME/CFS patients died more frequently when activated, had swollen energy-producing structures (mitochondria), and in one severely ill patient, contained unusual fat-like accumulations. These cellular changes suggest that ME/CFS involves real, measurable damage to immune system function.

Impaired TRPM3-dependent calcium influx and restoration using Naltrexone in natural killer cells of myalgic encephalomyelitis/chronic fatigue syndrome patients.

Eaton-Fitch, Natalie, Du Preez, Stanley, Cabanas, Hélène et al.·Journal of translational medicine·2022

This study found that immune cells called natural killer cells in ME/CFS patients have a broken calcium channel (TRPM3) that prevents them from working properly. When researchers treated these cells overnight with a drug called naltrexone, the calcium channel started working better and the immune cells functioned more like those from healthy people. This suggests that ME/CFS may involve faulty ion channels and that naltrexone could potentially help restore immune cell function.

EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.

Cox, Brandon S, Alharshawi, Khaled, Mena-Palomo, Irene et al.·JCI insight·2022

This study found that some people with ME/CFS have abnormal immune responses linked to past infections with Epstein-Barr virus (EBV) and human herpesvirus 6A (HHV-6A). The researchers discovered that proteins from these viruses may trigger the immune system to produce excess amounts of certain signaling molecules, leading to confused immune cell behavior. This suggests a possible biological mechanism for how these common viruses might contribute to ME/CFS symptoms in some patients.

Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis.

Nishi, Kensuke, Yoshimoto, Shohei, Nishi, Soichiro et al.·International journal of molecular sciences·2022

This study looked at a Japanese treatment called Epipharyngeal Abrasive Therapy (EAT) that targets chronic inflammation in the epipharynx (the area behind your nasal cavity). The researchers found that patients who received EAT had significantly lower levels of IL-6, a key inflammatory molecule linked to ME/CFS symptoms, compared to those who didn't receive the treatment. This suggests that reducing inflammation in this specific area might help improve systemic symptoms in ME/CFS and similar conditions.

E3 PreliminaryCohortPEM not requiredCase-Control

New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition.

Gavrilova, Natalia, Soprun, Lidiia, Lukashenko, Maria et al.·Pathophysiology : the official journal of the International Society for Pathophysiology·2022

This study describes a pattern found in some people who developed fibromyalgia (widespread pain) after COVID-19 infection. The researchers noticed that young women with loose, flexible joints who had COVID-19 and a specific tendon injury were more likely to develop fibromyalgia along with signs of inflammation. The study presents three patient cases that fit this pattern, suggesting COVID-19 may trigger fibromyalgia in people whose connective tissues are already prone to damage.

Immune SystemLong COVID Overlap

E3 PreliminaryPEM not required

An Unexpected Journey: The Lived Experiences of Patients with Long-Term Cognitive Sequelae After Recovering from COVID-19.

Loft, Mia I, Foged, Eva M, Koreska, Mai·Qualitative health research·2022

This study listened to people who experienced long-lasting thinking and memory problems after recovering from COVID-19. Patients described how these cognitive symptoms disrupted their daily lives, work, and relationships, and left them feeling anxious and uncertain about their future. The researchers suggest that doctors and researchers could learn from how people with similar conditions—like ME/CFS—manage their symptoms while waiting for treatments.

Cognitive Impairment

E3 PreliminaryPEM unclear

The circuit of symbolic violence in chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) (I): A preliminary study.

Gimeno Torrent, Xavier·Health care for women international·2022

This study examined letters written by ME/CFS patients to Spanish newspapers to understand why such a serious illness affecting millions remains poorly recognized by the public. The researchers found 13 different ways that society dismisses or ignores ME/CFS patients—including treating them with disrespect, refusing proper medical care, and making their illness invisible in public discussion. These patterns of dismissal work together to keep ME/CFS hidden and misunderstood.

Serum of Post-COVID-19 Syndrome Patients with or without ME/CFS Differentially Affects Endothelial Cell Function In Vitro.

Flaskamp, Lavinia, Roubal, Constanze, Uddin, Steven et al.·Cells·2022

This study examined blood samples from people with long COVID and those who developed ME/CFS after COVID-19, comparing them to healthy controls. Researchers tested whether certain proteins in these blood samples could harm the cells that line blood vessels. They found that the blood of ME/CFS patients contained more of these harmful proteins, and the blood samples from both patient groups affected blood vessel cells in different ways that could contribute to the fatigue and other symptoms these patients experience.

Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome.

Mahroum, Naim, Shoenfeld, Yehuda·Pathophysiology : the official journal of the International Society for Pathophysiology·2022

This article suggests that several chronic conditions—including ME/CFS, fibromyalgia, long COVID, and complex regional pain syndrome—may share a common cause: the immune system mistakenly producing antibodies that attack the autonomic nervous system (the part of your body that controls automatic functions like heart rate and blood pressure). The authors propose calling these conditions "autoimmune autonomic dysfunction syndromes" to highlight this shared mechanism and potentially help doctors diagnose and treat them more effectively.

Autonomic Nervous System

Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis/chronic fatigue syndrome patients.

Sasso, Etianne Martini, Muraki, Katsuhiko, Eaton-Fitch, Natalie et al.·Molecular medicine (Cambridge, Mass.)·2022

This study examined a specific ion channel called TRPM3 in immune cells from patients with ME/CFS and long COVID, comparing them to healthy people. Researchers found that both ME/CFS and long COVID patients had similar problems with how this ion channel functions. The findings suggest that broken ion channels might be part of why these conditions cause long-lasting fatigue and other symptoms.