Evidence browser

E2 ModerateCohortPEM unclearObservational

Chronic overlapping pain conditions in individuals with active opioid use disorder: a descriptive study of syringe program participants.

Rausch, Johnathan, Harte, Steven E, Williams, David A et al.·Journal of addictive diseases·2025

This study looked at how often chronic pain conditions occur together in people struggling with opioid addiction. Researchers found that people with opioid use disorder have much higher rates of several overlapping pain conditions—including ME/CFS, fibromyalgia, chronic migraines, and chronic back pain—than would be expected in the general population. Understanding this connection may help doctors treat both the pain and addiction more effectively.

Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study.

Steen, Olivier D, Bos, Martje, van Ockenburg, Sonja L et al.·BMC medicine·2025

This study found that ME/CFS, fibromyalgia, and irritable bowel syndrome tend to run in families alongside conditions like depression, anxiety, autoimmune diseases, and metabolic disorders. Researchers analyzed data from over 166,000 people in a Dutch population cohort to understand whether these conditions share common inherited risk factors. The findings suggest that the causes of functional disorders like ME/CFS may overlap with the causes of immune and metabolic diseases, which could point to new treatment approaches.

E2 ModerateCohortPEM requiredCross-Sectional

Understanding symptom clusters, diagnosis and healthcare experiences in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a cross-sectional survey in the UK.

Mansoubi, Maedeh, Richards, Thomas, Ainsworth-Wells, Martine et al.·BMJ open·2025

This large UK survey asked over 8,800 people with ME/CFS or long COVID about their symptoms and experiences with healthcare. The study found that fatigue, brain fog, pain, and sleep problems are the most common symptoms, but people often wait years for a diagnosis. Even after new healthcare guidelines were introduced, most patients said they weren't satisfied with the care they received from the NHS.

Immune SystemPost-Exertional Malaise

Clinical and Laboratory Characteristics of Fatigue-Dominant Long-COVID Subjects: A Cross-Sectional Study.

Lee, Jin-Seok, Choi, Yujin, Joung, Jin-Yong et al.·The American journal of medicine·2025

This study looked at 100 people with long COVID who experience significant ongoing fatigue, similar to ME/CFS. Researchers measured fatigue levels and checked blood levels of cortisol (a stress hormone) and other immune markers. They found that people with lower cortisol levels reported worse fatigue and lower quality of life, suggesting a possible connection between this hormone and fatigue severity.

Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome.

Collins Hutchinson, Meagan L, Liang, Emily, Fuster, Emily et al.·Autonomic neuroscience : basic & clinical·2025

This study looked at 84 women with connective tissue disorders (HSD/h-EDS) to understand how much autonomic nervous system problems they experience and how these affect their quality of life. The researchers found that these women had severe autonomic symptoms, with nearly 60% also having POTS and about 26% having ME/CFS. Overall, their quality of life was significantly worse than patients with other serious conditions like multiple sclerosis or rheumatoid arthritis.

Autonomic Nervous System

Chronic fatigue syndrome, depression, and anxiety symptoms due to relapsing-remitting multiple sclerosis are associated with reactivation of Epstein-Barr virus and Human Herpesvirus 6.

Maes, Michael, Almulla, Abbas F, Vojdani, Elroy et al.·Neuro endocrinology letters·2025

This study looked at whether reactivation of two common viruses—Epstein-Barr virus (EBV) and Human herpesvirus 6 (HHV-6)—are connected to fatigue, depression, and anxiety in people with a type of multiple sclerosis called RRMS. Researchers measured immune responses (antibodies) to these viruses in MS patients and healthy controls, and found that higher antibody levels were strongly linked to worse fatigue and mood symptoms. The findings suggest that when these dormant viruses become active in the body, they may trigger or worsen fatigue and psychiatric symptoms.

Genetic variants associated with chronic fatigue syndrome predict population-level fatigue severity and actigraphic measurements.

Liu, Patrick Z, Raizen, David M, Skarke, Carsten et al.·Sleep·2025

This study looked at whether the genetic factors that cause ME/CFS also influence fatigue levels in people without ME/CFS. Researchers compared movement patterns and body temperature rhythms in people with ME/CFS versus healthy controls, then checked if genetic variations linked to ME/CFS were also connected to fatigue in the general population. They found that people with ME/CFS showed significantly less movement and flatter daily temperature patterns, and some genetic variants associated with ME/CFS were also linked to fatigue symptoms in the broader population.

Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome.

Bastos, Victoria C, Greene, Kerrie A, Tabachnikova, Alexandra et al.·Journal of immunology (Baltimore, Md. : 1950)·2025

Researchers studied cerebrospinal fluid (the fluid around the brain and spinal cord) from people with ME/CFS and found that the immune system appears to work differently in different patients. They discovered two distinct patient groups with different immune patterns and pathogen exposure histories, even though both groups had similar symptoms. This suggests that ME/CFS may not be a single disease, but rather several related conditions with different underlying causes.

BiomarkersImmune System

Leveraging Explainable Automated Machine Learning (AutoML) and Metabolomics for Robust Diagnosis and Pathophysiological Insights in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Yagin, Fatma Hilal, Colak, Cemil, Al-Hashem, Fahaid et al.·Diagnostics (Basel, Switzerland)·2025

Researchers used advanced computer learning and blood tests to find chemical markers that could help diagnose ME/CFS. They analyzed 888 different chemicals in blood samples from 106 ME/CFS patients and 91 healthy people, and found a pattern of chemical imbalances that correctly identified ME/CFS patients 87% of the time. The key chemical imbalances involved energy production in cells, inflammation, and gut health—areas that have long been suspected in ME/CFS.

Energy Metabolism

Awareness and Perception of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Among Pain Specialists: A Questionnaire-Based Study.

Uygun, Gürsan Güneş, Gözükızıl, Salim Taner, Bilen, Ayşegül·Cureus·2025

This study asked pain doctors in Turkey about their knowledge of ME/CFS and how they evaluate and treat patients with the condition. The results show that many pain specialists aren't familiar with ME/CFS, and some hold misconceptions—like thinking it's a type of depression or that intense exercise will help. This matters because pain doctors could potentially help ME/CFS patients, but they need better education about the condition first.

Autonomic Nervous System

An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques.

Germain, Arnaud, Jaycox, Jillian R, Emig, Christopher J et al.·International journal of molecular sciences·2025

This study looked for specific immune proteins called autoantibodies in the blood of ME/CFS patients to see if they might be causing the illness. Researchers tested over 7,500 different immune markers using advanced laboratory techniques in 172 people. Surprisingly, they did not find significant differences in autoantibodies between ME/CFS patients and healthy controls, though they did notice some subtle patterns between men and women with ME/CFS that warrant further investigation.

Medication use and symptomology in North American women with myalgic encephalomyelitis/chronic fatigue syndrome.

Pochakom, Angela, MacNevin, Gillian, Madden, Robyn F et al.·Frontiers in medicine·2025

This study surveyed 135 women with ME/CFS in North America to understand what medications they use and how these relate to their symptoms and daily functioning. Most participants were taking an average of 3 medications for ME/CFS-related symptoms, with pain medications being the most common, followed by psychiatric and immune-related medications. Interestingly, the study found a U-shaped pattern: both people using very few medications and those using many medications reported lower physical functioning, while moderate medication use was associated with better functioning.

Interventions

Abnormal T-Cell activation and cytotoxic T-Cell frequency discriminate symptom severity in myalgic encephalomyelitis/chronic fatigue syndrome.

Lee, Ji-Sook, Lacerda, Eliana, Kingdon, Caroline et al.·Journal of translational medicine·2025

This study compared immune system profiles in 96 ME/CFS patients with either mild/moderate or severe disease. Researchers found that people with severe ME/CFS had more activated immune cells and higher levels of inflammatory chemicals, while those with milder disease showed different patterns suggesting their bodies were responding to chronic viral infection. These findings suggest that mild and severe ME/CFS may involve different underlying immune problems, which could eventually help doctors predict disease severity and develop targeted treatments.

E2 ModerateCohortPEM requiredCross-Sectional

Patient-reported treatment outcomes in ME/CFS and long COVID.

Eckey, Martha, Li, Peng, Morrison, Braxton et al.·Proceedings of the National Academy of Sciences of the United States of America·2025

This study asked nearly 4,000 ME/CFS and long COVID patients about their experiences with over 150 different treatments to see which ones helped them feel better. The researchers found that ME/CFS and long COVID are very similar illnesses with overlapping symptoms and that patients with each condition responded similarly to treatments. The study also discovered that different patient subgroups—like those with heart rate and blood pressure problems, or those with thinking and memory problems—benefited most from specific types of treatments.

E2 ModerateCohortPEM unclearRegistry-Resource

Unequal access to diagnosis of myalgic encephalomyelitis in England.

Samms, Gemma Louise, Ponting, Chris P·BMC public health·2025

This study examined NHS records from England to understand how many people have ME/CFS and whether diagnosis is fair across different groups. Researchers found that about 100,000 people in England have been officially diagnosed with ME/CFS, but the actual number may be much higher—around 404,000 in the UK. The diagnosis rates varied significantly depending on gender, age, ethnicity, and where people live, suggesting some patients are being missed.

Diagnostics

E2 ModerateBehavioralPEM unclearCross-Sectional

Psychosocial Nursing Diagnoses of Individuals With Myalgic Encephalomyelitis-Chronic Fatigue Syndrome: A Descriptive Study.

Oter-Quintana, Cristina, Alameda-Cuesta, Almudena, Brito-Brito, Pedro Ruymán et al.·Nursing open·2025

This study looked at the emotional and psychological challenges that people with ME/CFS commonly experience. Researchers surveyed 48 adults with ME/CFS and found that most experienced feelings of powerlessness, difficulty coping, and fear. The study identified three different groups of patients: one group with more severe symptoms and greater emotional distress, and two other groups with milder symptoms who were still working or retired.

Abnormal breathing patterns and hyperventilation are common in patients with chronic fatigue syndrome during exercise.

Mancini, Donna M, Brunjes, Danielle L, Cook, Dane et al.·Frontiers in medicine·2025

Researchers studied how patients with ME/CFS breathe during exercise and found that many breathe abnormally in ways that healthy people do not. Specifically, 42% of ME/CFS patients showed irregular breathing patterns, and 32% were breathing too fast and too deeply (hyperventilation). These breathing problems were much more common in ME/CFS patients than in the healthy control group, suggesting that abnormal breathing may be contributing to the fatigue and breathlessness patients experience.

BiomarkersEnergy Metabolism

Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis.

Rostami-Afshari, Bita, Elremaly, Wesam, McGregor, Neil R et al.·International journal of molecular sciences·2025

Researchers found that people with ME have lower levels of a kidney protein called SMPDL3B in their blood and urine compared to healthy people. This protein is important for keeping the kidney's filtering system working properly. The study also identified several metabolic imbalances in ME patients' blood that are linked to kidney problems. These findings suggest that kidney function may be affected in ME, and this protein could potentially be used as a simple blood test to help understand the disease.

Autonomic Nervous SystemCognitive Impairment

Characterization of Postural Orthostatic Tachycardia Syndrome in Long COVID: Self-reported Data From the LISTEN Study.

Al Mouslmani, Mohammad, Sawano, Mitsuaki, Arun, Adith S et al.·JACC. Advances·2025

This study looked at people with long COVID who also developed POTS (a condition where the heart rate spikes when standing up). Among nearly 600 long COVID patients, about 29% reported having POTS. People with both conditions reported significantly more symptoms—including dizziness, chest pain, extreme fatigue, difficulty exercising, and brain fog—and experienced worse overall health and quality of life compared to those with long COVID alone.

E2 ModerateCohortPEM requiredObservational

Low-dose rapamycin alleviates clinical symptoms of fatigue and PEM in ME/CFS patients via improvement of autophagy: a pilot study.

Ruan, Brian T, Bulbule, Sarojini, Gile, Brooke et al.·Journal of translational medicine·2025

Researchers tested a low-dose drug called rapamycin in 86 ME/CFS patients to see if it could reduce fatigue and post-exertional malaise (PEM). About 74% of patients who completed the first month showed improvements in fatigue, PEM, and other symptoms, and the drug appeared safe with no serious side effects. The study suggests that rapamycin may work by fixing a cellular process called autophagy, which appears to be broken in ME/CFS patients.