Evidence browser

E2 ModerateCohortPEM requiredObservational

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.

Low Vasopressin in Myalgic Encephalomyelitise/Chronic Fatigue Syndrome.

Huhmar, Helena M, Soinne, Lauri S, Bertilson, Bo Christer et al.·Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·2025

This study found that most people with ME/CFS have abnormally low levels of vasopressin, a hormone that helps your body control water balance and blood volume. The researchers measured this hormone and fluid markers in over 100 ME/CFS patients and discovered that 82% had vasopressin levels below the detectable range. This may help explain why many ME/CFS patients experience excessive thirst, frequent urination, and dizziness when standing up.

Circulating cell-free RNA signatures for the characterization and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome.

Gardella, Anne E, Eweis-LaBolle, Daniel, Loy, Conor J et al.·Proceedings of the National Academy of Sciences of the United States of America·2025

Researchers analyzed tiny pieces of RNA floating in the blood of people with ME/CFS and compared them to healthy people. They used a computer program to identify a pattern of these RNA pieces that could help diagnose ME/CFS with 77% accuracy. The study found that people with ME/CFS have different levels of immune cells releasing material into their blood, suggesting the immune system is behaving differently.

Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA.

Issa, Anindita, Lin, Jin-Mann S, Chen, Yang et al.·Journal of clinical medicine·2025

This study found that people with ME/CFS experience much higher levels of autonomic nervous system problems—which control things like heart rate, blood pressure, and digestion—compared to healthy people. Nearly all ME/CFS patients (97%) had at least one autonomic symptom, with common complaints including dizziness, cold hands and feet, and difficulty standing up. The more autonomic symptoms someone had, especially in certain areas like blood pressure regulation and stomach problems, the more severe their overall illness tended to be.

E2 ModerateCohortPEM not requiredCase-Control

Possible Racial Disparities in the Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Jones, Chloe Lisette, Younger, Jarred·International journal of environmental research and public health·2025

This study looked at whether Black people and other racial minorities with ME/CFS symptoms are less likely to receive an official diagnosis compared to white people. Researchers surveyed over 1,100 people and found that white respondents were nearly three times more likely to be diagnosed with ME/CFS than non-white respondents, even when they had similar symptoms. The findings suggest that racial bias may be affecting who gets diagnosed with ME/CFS.

Alterations in gut microbiota and associated metabolites in patients with chronic fatigue syndrome.

Cheng, Xinxin, Wang, Wenkuan, Xu, Tingting et al.·Scientific reports·2025

This study looked at the bacteria living in the gut of people with ME/CFS compared to healthy people, and found that ME/CFS patients have fewer types of bacteria and lower levels of helpful compounds called short-chain fatty acids (SCFAs) that bacteria produce. The study found that people with ME/CFS who eat more fiber have higher levels of these beneficial compounds, suggesting diet may help restore some of the bacterial imbalances seen in ME/CFS.

Energy Metabolism

E2 ModerateCohortPEM unclearObservational

Hippocampal subfield volume alterations and associations with severity measures in long COVID and ME/CFS: A 7T MRI study.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie et al.·PloS one·2025

Researchers used advanced brain imaging to compare a part of the brain called the hippocampus in long COVID patients, ME/CFS patients, and healthy people. They found that certain areas of the hippocampus were larger in both patient groups compared to healthy controls, and these size differences were linked to how severe symptoms like fatigue, pain, and memory problems were. This suggests that changes in brain structure might explain some of the cognitive difficulties these patients experience.

Cognitive Impairment

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.

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.

E2 ModerateCohortPEM unclearLongitudinal

Functional olfactory impairment and fatigue in post-COVID-19 syndrome including ME/CFS - a longitudinal prospective observational study.

Meyer-Arndt, Lil, Pierchalla, Greta, Mödl, Lukas et al.·Brain, behavior, & immunity - health·2025

This study followed 45 long-COVID patients over 28 months to understand the connection between smell problems and fatigue, including those who developed ME/CFS. Researchers tested how well patients could smell (detecting scent strength, telling scents apart, and identifying them) and measured their fatigue, thinking ability, and physical strength. Most patients' smell improved over time, but problems with identifying specific smells lasted the longest, and patients with better smell discrimination at the start tended to feel better and function better after 20 months.

Cognitive Impairment

E2 ModerateCohortPEM not requiredCross-Sectional

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.

Autonomic Nervous SystemCognitive Impairment

E2 ModerateBehavioralPEM not requiredObservational

Efficacy of Eszopiclone Plus Acupuncture Therapy by Dispersing the Stagnated Liver-Qi and Regulating the Spirit for Treating Chronic Fatigue Syndrome-Related Sleep Disorders.

Huang, Bing, Geng, Yining, Liu, Lanlan·Psychiatry and clinical psychopharmacology·2025

This study looked at whether adding acupuncture to a sleep medication (eszopiclone) could help people with ME/CFS who struggle with sleep. Researchers compared 57 patients who received both the medication and acupuncture to 50 patients who received only the medication. The combined treatment group had better sleep quality, higher levels of chemicals in the blood that support mood and brain health, and fewer side effects.

Sleep

Provocation of brachial plexus and systemic symptoms during the elevated arm stress test in individuals with myalgic encephalomyelitis/chronic fatigue syndrome or idiopathic chronic fatigue.

Edwards, Charles C, Byrnes, Julia M, Broussard, Camille A et al.·Journal of translational medicine·2025

Researchers tested whether a simple arm position exercise (holding arms overhead and opening/closing fists) could trigger symptoms in ME/CFS patients who struggle with overhead activities. They found that nearly all patients (97%) developed arm symptoms like pain, numbness, or heaviness during the test, and 41% also experienced whole-body symptoms like dizziness, brain fog, or a racing heart. This suggests that some ME/CFS patients may have nerve compression issues in their shoulders or neck that worsen with certain arm positions.

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 not requiredCross-Sectional

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.

Pain and SensitizationCognitive Impairment

The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Oosterman, Joukje M, van der Schaaf, Marieke, de Kleijn, Willemien P E et al.·Journal of psychosomatic research·2025

This study looked at how fatigue and pain affect thinking and memory problems in people with ME/CFS. Researchers tested 1,375 patients on tasks like reaction time and attention, and found that both fatigue severity and pain severity were linked to worse cognitive performance. The effects were stronger in older patients, suggesting that age may play a role in how much fatigue and pain impact thinking abilities.

E2 ModerateCohortPEM not requiredCase-Control

Diagnosis of chronic fatigue syndrome using beat-to-beat autonomic measurements.

Kujawski, Sławomir, Tabisz, Hanna, Morten, Karl J et al.·Journal of translational medicine·2025

Researchers used artificial intelligence to analyze how the heart and nervous system behave differently in ME/CFS patients compared to healthy people. By measuring heart rate changes beat-by-beat, they found a pattern that could identify ME/CFS patients with 89% accuracy. The key differences included a less responsive vagal nerve (which normally calms the body), a more active stress response in blood vessels, and less efficient heart pumping.

E2 ModerateBehavioralPEM unclearCase-Control

Bipolar spectrum, hypothyroidism, and their association with chronic fatigue/myalgic encephalomyelitis-like syndrome in long COVID: could they be identified as early determinants?

Tusconi, Massimo, Dursun, Serdar M, Pegreffi, Francesco et al.·Frontiers in psychiatry·2025

This study found that people with long COVID who developed ME/CFS-like symptoms were much more likely to have had hypothyroidism (an underactive thyroid) or bipolar spectrum disorders before getting sick compared to people from before the pandemic. The researchers suggest these pre-existing conditions might make someone more vulnerable to developing ME/CFS after COVID-19, possibly because they affect sleep rhythms and immune function.

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.

Post-Exertional Malaise