Evidence browser

Oral minocycline therapy as first-line treatment in patients with Myalgic encephalomyelitis and long COVID: A pilot study.

Miwa, Kunihisa·eNeurologicalSci·2025

This small study looked at whether a common antibiotic called minocycline might help people with ME/CFS, including those with long COVID. Fifty-five patients took minocycline for about 6 weeks, and 80% of those who completed the treatment reported meaningful improvements in their symptoms like fatigue, brain fog, and sleep problems. The treatment worked best for people early in their illness (within 6 months of symptom onset).

E2 ModerateCohortPEM not requiredObservational

Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment.

Smith, Steven J, Smith, B Holly, Sichlau, Michael J et al.·Phlebology·2025

This study looked at 45 women with chronic pelvic pain caused by abnormal blood pooling in pelvic veins. These patients experienced many symptoms beyond pelvic pain—including brain fog, fatigue, migraines, constipation, and anxiety. After receiving a catheter-based procedure to fix the blood pooling, most of these systemic symptoms improved significantly (by 50% or more).

Pain and SensitizationAutonomic Nervous SystemCognitive Impairment

Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia.

Azimi, Ghazaleh, Elremaly, Wesam, Elbakry, Mohamed et al.·International journal of molecular sciences·2025

This study measured a protein called FGF-21 in the blood of people with ME/CFS, fibromyalgia, and both conditions combined, then compared how their symptoms and thinking abilities differed based on their FGF-21 levels. The researchers found that FGF-21 levels—not just the diagnosis alone—were better at predicting which symptoms and cognitive problems each person would experience. This suggests FGF-21 could become a useful blood test to help doctors understand and treat these conditions more precisely.

Physical activity and sedentariness levels in patients with post-exertional malaise resulting from post-COVID-19 syndrome.

Elkebir, Kamel-Eddine, Gilbert, Jo-Anne, Kugathasan, Thiffya Arabi et al.·Work (Reading, Mass.)·2025

This study looked at how physical activity changed in 154 people who developed post-exertional malaise (PEM)—extreme tiredness and pain that worsens after activity—following COVID-19. Researchers found that after COVID-19, these patients became much less active and spent more time sitting, especially at work. Women and those with more severe PEM were most affected by these changes.

E2 ModerateBehavioralPEM not requiredObservational

Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort.

Bos, Martje, Monden, Rei, Wray, Naomi R et al.·Psychological medicine·2025

This study looked at whether ME/CFS, irritable bowel syndrome, and fibromyalgia run in families, and whether they share common causes with depression and anxiety disorders. Researchers studied over 150,000 people in the Netherlands and found that these conditions do tend to cluster in families—if a relative has one of these conditions, your risk of having it is higher. ME/CFS showed the strongest family connection and was most closely linked to depression.

Poor Association Between Clinical Characteristics and Seropositivity in Children With Suspected Long COVID-A Single-Centre Study.

Olsson-Åkefeldt, S, Luthander, J, Anmyr, L et al.·Acta paediatrica (Oslo, Norway : 1992)·2025

This study looked at 113 children and teenagers who visited a specialized clinic for suspected long COVID symptoms. The researchers found that about half of the children had antibodies showing they had been infected with SARS-CoV-2, while the other half did not. Most children reported multiple symptoms like fatigue, dizziness, difficulty concentrating, and nausea, and these symptoms were similar whether or not they had evidence of past COVID infection. Many children were missing school and had to stop doing activities they enjoyed.

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 ModerateCohortPEM not requiredCase-Control

In transfusion-dependent thalassemia, neuronal damage biomarkers are associated with affective and chronic fatigue symptoms.

Ridhaa, Maha Abdul Saheb, Al-Hakeim, Hussein Kadhem, Kahlol, Mohammed K et al.·Scientific reports·2025

This study looked at children with thalassemia, a blood disorder requiring frequent transfusions, to see if brain damage and inflammation might cause depression, anxiety, and chronic fatigue. Researchers measured specific markers of brain injury and inflammation in the blood and found that children with thalassemia had higher levels of these markers and more fatigue and mood symptoms than healthy children. The study suggests that iron buildup from transfusions may damage nerve cells in the brain, leading to these symptoms.

Neuroinflammation

E2 ModerateCohortPEM requiredObservational

The Clinical Relevance of Mast Cell Activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Rohrhofer, Johanna, Ebner, Lilian, Schweighardt, Johannes et al.·Diagnostics (Basel, Switzerland)·2025

This study looked at whether mast cells—immune cells that release chemicals causing inflammation—play a role in ME/CFS. Researchers surveyed 687 ME/CFS patients and reviewed records from 383 others, finding that about 25% had signs of problematic mast cell activation. Importantly, patients with mast cell problems who received targeted treatment reported better symptom relief than those without mast cell involvement, suggesting this might be a treatable subtype of ME/CFS.

Immune SystemPost-Exertional Malaise

E2 ModerateCohortPEM unclearLongitudinal

Characterization of Post-Viral Infection Behaviors Among Patients With Long COVID: Prospective, Observational, Longitudinal Cohort Analyses of Fitbit Data and Patient-Reported Outcomes.

Zhang, Tianmai M, Sharp, Sydney P, Scott, John D et al.·JMIR formative research·2025

Researchers gave 82 people with long COVID or ME/CFS Fitbit devices to track their physical activity, heart rate, and sleep for up to a year, while also asking them to report how they felt. They found that people who were less physically active reported worse fatigue, breathing problems, and physical function, and their symptoms worsened over time compared to those who remained more active. This suggests that activity levels may be related to symptom severity in long COVID, though the study couldn't prove that low activity causes worse symptoms.

Sleep

E2 ModerateCohortPEM not requiredCross-Sectional

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

E2 ModerateCohortPEM not requiredCross-Sectional

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.

A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.

Hirsch, Annemarie G, Justice, Anne E, Poissant, Amy et al.·BMC infectious diseases·2025

Researchers studied the genes of people who had Lyme disease to understand why some develop lasting symptoms even after treatment. They found two genetic regions that might be involved in persistent Lyme disease symptoms, with one linked to a protein called MARC2 that affects immune function. When they checked whether these same genetic changes appeared in people with fibromyalgia or ME/CFS, they did not find the same patterns, suggesting these conditions may have different genetic roots.

Immune System

Age-specific alterations of the gut mycobiome in patients with myalgic encephalomyelitis/chronic fatigue syndrome and identification of potential diagnostic biomarkers.

Gan, Yunong, Ning, Ruihong, Zhang, Wen et al.·BMC microbiology·2025

Researchers studied fungi living in the gut of ME/CFS patients compared to healthy people across different age groups. They found that people with ME/CFS have different types and amounts of gut fungi than healthy people, and these differences vary depending on age. Using these fungal patterns, they could identify ME/CFS patients with high accuracy—especially when looking at people of similar ages—suggesting gut fungi might help diagnose the condition.

Biomarkers

E2 ModeratePEM unclearBiobank-Resource

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.

Immune System

Defining a High-Quality Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cohort in UK Biobank.

Samms, Gemma L, Ponting, Chris P·NIHR open research·2025

This study looked at how ME/CFS is identified in UK Biobank, a large database of health information from hundreds of thousands of people. Researchers found that about 1 in 100 UK Biobank participants had some evidence of ME/CFS, but only about one-third had strong, consistent evidence across multiple records. When they accounted for people too ill to participate in the study, they estimated that around 410,000 people in the UK have ME/CFS.

Diagnostics

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.

E2 ModerateCohortPEM not requiredCross-Sectional

Post-COVID-19 Condition Risk Factors and Symptom Clusters and Associations With Return to Pre-COVID-19 Health-Results From a 2021 Multistate Survey.

Konkle, Stacey L, Magleby, Reed, Bonacci, Robert A et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2025

This study looked at nearly 30% of people who had COVID-19 in 2020 and developed long-term symptoms afterward (post-COVID condition). Among those with ongoing symptoms, about 77% had not fully recovered to their pre-COVID health 2-15 months later. The researchers found that certain symptom patterns—especially fatigue similar to ME/CFS, upper respiratory problems, and digestive issues—were most strongly linked to prolonged recovery.

Assessing the influence of lived-experience experts on healthcare providers in a virtual community of practice: a qualitative study.

Weaver, Stephanie Sargent, Carry, Monique, Bertolli, Jeanne et al.·Frontiers in health services·2025

This study looked at whether having patients with lived experience of Long COVID and ME/CFS help teach doctors made a real difference in patient care. Researchers tracked what these patient-experts recommended to doctors through online training sessions from 2022-2024, and then asked actual patients if their doctors seemed to apply that advice. The main recommendations focused on validating patients' experiences, showing empathy, helping with referrals, and supporting self-care. Patients reported noticing positive changes in how their doctors treated them, suggesting that including patient-experts in medical education actually works.

Diagnostics