Evidence browser

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.

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.

Absence of BOLD adaptation in chronic fatigue syndrome revealed by task functional MRI.

Schönberg, Laura, Mohamed, Abdalla Z, Yu, Qiang et al.·Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism·2025

This study looked at how the brain responds when people with ME/CFS do mental tasks, using brain imaging to measure blood flow. Researchers found that while healthy people's brains become more efficient with repeated effort (showing less activation over time), people with ME/CFS showed the opposite pattern—their brains actually increased activity with each repetition. This suggests that ME/CFS may involve a fundamental difference in how the brain adapts to mental work, potentially explaining why cognitive tasks feel so exhausting.

E2 ModerateCohortPEM unclearCase-Control

People with Long Covid and ME/CFS Exhibit Similarly Impaired Balance and Physical Capacity: A Case-Case-Control Study.

Hayes, Lawrence D, Sanal-Hayes, Nilihan E M, Mclaughlin, Marie et al.·The American journal of medicine·2025

This study compared balance and physical strength in people with long COVID, people with ME/CFS, and healthy volunteers. Both long COVID and ME/CFS patients showed significantly worse balance during standing and took longer to perform simple physical tasks like standing up from a chair compared to healthy people. Importantly, the balance and strength problems were equally severe in both groups, despite long COVID being a much newer illness.

E2 ModerateCohortPEM requiredLongitudinal

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.

Autonomic Nervous System

Temporal Dynamics of the Plasma Proteomic Landscape Reveals Maladaptation in ME/CFS Following Exertion.

Germain, Arnaud, Glass, Katherine A, Eckert, Melissa A et al.·Molecular & cellular proteomics : MCP·2025

Researchers studied what happens in the blood of ME/CFS patients during and after exercise to understand post-exertional malaise (PEM)—the worsening of symptoms that occurs after physical activity. They measured over 6,000 different proteins in 79 ME/CFS patients and 53 healthy controls before exercise, immediately after, and during recovery. They found that ME/CFS patients have abnormal protein changes during recovery that suggest their immune system and energy-producing cells are not working properly after exertion.

Immune SystemPost-Exertional Malaise

Comparative Study Between Cognitive Phenotypes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Multiple Sclerosis.

Aoun Sebaiti, Mehdi, Oubaya, Nadia, Gounden, Yannick et al.·Diagnostics (Basel, Switzerland)·2025

This study compared thinking and memory problems in ME/CFS patients with those in multiple sclerosis (MS) patients, since both conditions can cause similar cognitive issues, fatigue, and pain. Researchers tested 40 people with ME/CFS and 40 with MS using standard memory and attention tests. They found that ME/CFS patients have a specific pattern of cognitive difficulties, particularly problems with consolidating (storing) new information in memory, which is distinct from MS.

E2 ModerateCohortPEM requiredCase-Control

The Relation Between Cardiac Output and Cerebral Blood Flow in ME/CFS Patients with a POTS Response During a Tilt Test.

van Campen, C Linda M C, Visser, Frans C·Journal of clinical medicine·2025

When people with ME/CFS and POTS stand up, their blood pressure and heart rate don't respond normally, causing symptoms like dizziness and fatigue. This study looked at 260 ME/CFS patients during a tilt test to understand how the heart's output of blood relates to blood flow in the brain. The researchers found two different patterns: about two-thirds of patients showed their brain blood flow dropped at roughly the same rate as their heart's output decreased, while about one-third had a different pattern where their heart was racing but their heart output wasn't dropping as much, and their brain blood flow didn't follow the expected pattern.

Autonomic Nervous System

Haptoglobin phenotypes and structural variants associate with post-exertional malaise and cognitive dysfunction in myalgic encephalomyelitis.

Moezzi, Atefeh, Ushenkina, Anastasiya, Widgren, Anna et al.·Journal of translational medicine·2025

Researchers studied a protein called haptoglobin in people with ME/CFS and found it may be connected to post-exertional malaise (that worsening of symptoms after activity) and brain fog. They discovered that certain genetic variations of this protein were more common in ME/CFS patients, and those variations were linked to worse symptoms and cognitive problems. The study suggests haptoglobin could be a useful marker to help doctors understand why ME/CFS symptoms vary between patients.

BiomarkersPost-Exertional Malaise

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 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.

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.

E2 ModerateCohortPEM requiredCross-Sectional

Concentrations of uremic bacterial metabolites in patients with post-COVID-19 syndrome.

Brigo, Natascha, Mayr, Wolfram, Taenzer, Maja et al.·Frontiers in cellular and infection microbiology·2025

This small study looked at special waste products made by gut bacteria in the urine of people with long COVID, ME/CFS, and healthy people. Researchers found that people with long COVID and ME/CFS had different patterns of these bacterial products compared to healthy controls, and these patterns might be connected to their symptoms like fatigue and post-exertional malaise (feeling much worse after activity).

E2 ModerateDiagnosticPEM unclearCross-Sectional

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.

Immune System

Psychometric evaluation of the PROMIS® physical function short form 12a for use by adults with myalgic encephalomyelitis/chronic fatigue syndrome.

Yang, Manshu, Keller, San, Rafiee, Parisa et al.·Health and quality of life outcomes·2025

Researchers tested whether a questionnaire called PROMIS Physical Function Short Form (PF-SF) works well for measuring how much ME/CFS affects a person's ability to do physical activities. They asked 173 people with ME/CFS and 161 healthy people to complete the questionnaire and found that it accurately captured the differences in physical ability between the two groups. The questionnaire appears to be a reliable and useful tool for doctors and researchers to measure physical function in people with ME/CFS.

Predisposing and Precipitating Factors in Epstein-Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Jason, Leonard A, Katz, Ben Z·Microorganisms·2025

This study followed college students before and after they got infectious mononucleosis (IM) caused by Epstein-Barr virus to understand why some people develop ME/CFS afterward while others recover. Researchers collected health information and blood samples from students at three time points: before they got sick, shortly after their IM diagnosis, and six months later. By studying these young people over time, the researchers identified certain factors present before and during the infection that seemed to predict who would develop ME/CFS rather than recover.

Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie et al.·The American journal of medicine·2025

Researchers used advanced brain imaging to measure chemical imbalances in ME/CFS and long COVID patients compared to healthy people. They found that two important brain chemicals—glutamate and N-acetyl-aspartate—were significantly higher in patients with both conditions. These chemical imbalances were connected to how severe patients' symptoms were, suggesting that abnormal brain chemistry may play a role in the exhaustion and other symptoms these patients experience.

Neuroinflammation

E2 ModerateCohortPEM unclearLongitudinal

Variation in Repeated Handgrip Strength Testing Indicates Submaximal Force Production in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Popkirov, Stoyan·European journal of neurology·2025

This study looked at handgrip strength tests in ME/CFS patients and healthy people to understand why grip strength varies so much in ME/CFS. Researchers found that ME/CFS patients showed more inconsistency in their grip strength measurements compared to healthy controls, suggesting their bodies aren't producing maximum force even when asked to do so. This pattern indicates the problem may be related to how the brain controls muscles rather than the muscles themselves being permanently damaged.

Biomarkers

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 required

Two neurocognitive domains identified for patients with myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of COVID-19.

Sandoval, Ariadna, Li, Mingqi, Jason, Leonard A·Frontiers in neurology·2025

This study looked at brain-related symptoms in over 2,600 people with ME/CFS and COVID long-haul (PASC), finding that their cognitive problems fall into two main categories. The first group includes classic memory and concentration difficulties, while the second group involves being overwhelmed by sensory input like loud noises or bright lights. The research suggests that doctors and researchers should pay more attention to sensory overload as an important part of cognitive problems in these conditions.