ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

61–80 of 402 studies

Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: a randomized, double-blind, placebo-controlled, crossover study.

Smith, Simon, Sullivan, Karen·International journal of behavioral medicine·2003

This study tested whether cognitive problems (like difficulty concentrating) in people with ME/CFS are caused by actual chemical exposure or by what people believe they are being exposed to. Thirty-six patients were given either a placebo or a chemical trigger while not knowing which one they received, and their thinking ability was tested before and after. The results showed that cognitive performance got worse when patients thought they had been exposed to a chemical, regardless of what they actually received.

Cognitive Impairment

E1 ReplicatedTrialPEM not requiredMechanistic

Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal.

Morriss, Richard K, Robson, Michael J, Deakin, J F William·Psychopharmacology·2002

This study tested whether people with ME/CFS have unusually sensitive brain receptors that respond to a hormone-like drug called clonidine. Researchers gave 10 ME/CFS patients and 10 healthy controls either clonidine or a placebo while they performed stressful thinking tasks, and measured their hormones, blood pressure, and thinking speed. ME/CFS patients showed slightly stronger hormone responses to clonidine and were faster at starting a planning task, suggesting their brains may react more strongly to stress-related chemical signals.

Cognitive Impairment

E1 ReplicatedTrialPEM not requiredRCT

An assessment of cognitive function and mood in chronic fatigue syndrome.

Marshall, P S, Watson, D, Steinberg, P et al.·Biological psychiatry·1996

This study tested whether ME/CFS affects how quickly people think and process information, how fast they can move, and their mood. Researchers gave patients cognitive tests and mood surveys before and after treatment with either an active medication or placebo. They found that people with ME/CFS were slower at thinking tasks and had more difficulty experiencing positive emotions, but their ability to focus and pay attention was not noticeably impaired.

Cognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Item comprehension and content coverage of patient-reported outcome measures for long COVID: a qualitative study.

Zigler, Christina K, Yousefian, Charis, Mangrum, Rikki et al.·Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation·2026

Researchers asked 30 adults with Long COVID to review four existing survey questionnaires to see if the questions were clear and relevant to their condition. Participants reported they could understand most questions and found them relevant to their experiences. The study also identified ways these surveys could be improved, such as simplifying instructions and shortening length. These are preliminary findings from one qualitative study, and further testing of these surveys is planned.

Autonomic Nervous SystemDiagnosticsCognitive ImpairmentPost-Exertional Malaise

E2 ModerateCohortPEM unclearLongitudinal

Two-timepoint multidomain follow-up of post-COVID condition and ME/CFS: overlapping autonomic, small-fiber, and cognitive changes.

Azcue, N, Barranco, C, Tijero-Merino, B et al.·Journal of translational medicine·2026

Researchers compared 21 people with post-COVID condition and 17 people with ME/CFS over about 2.5 years, measuring nerve function, autonomic symptoms, and cognitive performance. They observed that both groups showed similar patterns of changes over time—including worsening processing speed and cold sensation sensitivity, but improving heat sensation thresholds and verbal memory. While the two conditions appeared increasingly alike on follow-up testing, the study does not establish whether they are truly the same disease or simply share overlapping symptoms.

Pain and SensitizationAutonomic Nervous SystemDiagnosticsCognitive Impairment

E2 ModerateCohortPEM not requiredCross-Sectional

Symptom profiles and health-related quality of life in Korean adults with post-acute sequelae of SARS-CoV-2 infection (PASC): A latent profile analysis.

Kim, Su-Jin, Kim, Jinhee·PloS one·2026

This study examined symptom patterns in 629 Korean adults with long COVID (persistent symptoms ≥12 weeks after COVID-19). Researchers identified four distinct groups: people with few symptoms, moderate multi-body symptoms, fatigue and post-exertional malaise-dominant symptoms, and severe multi-body symptoms. Quality of life decreased substantially as symptom burden increased. The findings are observational and reflect one population; whether they apply to ME/CFS remains unclear.

DiagnosticsCognitive ImpairmentPost-Exertional Malaise

E2 ModerateBehavioralPEM not requiredCross-Sectional

Disentangling comorbidity: symptom dimensions of internalizing and functional disorders in a large general population sample.

Saini, Urvi, Aggen, Steven H, Oldehinkel, Albertine J et al.·BMC psychiatry·2026

This study looked at how symptoms of depression, anxiety, ME/CFS, fibromyalgia, and irritable bowel syndrome overlap in over 100,000 people. Researchers found that these conditions share common symptoms like fatigue, sleep problems, and difficulty concentrating—which they call 'general malaise'—rather than being completely separate diseases. Understanding these shared symptoms may help explain why people often have multiple conditions at the same time.

Pain and SensitizationCognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Assessment of dynamic cerebral blood flow changes during cognitive tasks in patients with post-COVID-19 syndrome.

Kutz, Dieter F, Garbsch, René, Mooren, Frank C et al.·Brain communications·2026

This study looked at how blood flow in the brain changes when people with post-COVID-19 syndrome try to do mental tasks. Researchers used special infrared cameras to watch blood flow in the thinking part of the brain while patients did concentration exercises. They found that people with post-COVID-19 had unusual, less flexible blood flow patterns compared to healthy people, which may help explain why they feel mentally tired and have trouble concentrating.

Cognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Symptom, Functional, and Work Participation Profiles Among Racialized Canadians with Pre-Existing Mental Health Challenges and Long COVID: A Cross-Sectional Study.

Shahzad, Maryam, Siddiqui, Sana, Lau, Chloe et al.·Healthcare (Basel, Switzerland)·2026

This study observed symptom burden, functional impairment, and mental health outcomes in 51 Canadian adults with long COVID who also identified as racialized and had pre-existing mental health conditions. Participants reported moderate overall symptoms, notable fatigue and post-exertional malaise, cognitive difficulties, and mild-to-moderate anxiety and depression, alongside moderate functional limitations in work, social, and daily activities. However, this is a small, self-selected group, and the findings may not generalise to all long COVID patients.

Cognitive ImpairmentLong COVID OverlapPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Microstructural alterations in brain tissue of ME/CFS and long COVID using diffusion tensor imaging and diffusion kurtosis imaging.

Singh, Tanoj Bahadur, Marshall-Gradisnik, Sonya, Barnden, Leighton et al.·Frontiers in medicine·2026

Researchers used specialized brain imaging scans (DTI and DKI) to observe differences in brain tissue structure between people with ME/CFS, people with long COVID, and healthy controls. They found that ME/CFS and long COVID showed microstructural changes in different brain regions, though the study is cross-sectional and cannot explain why these changes occur or what role they play in symptoms. These are preliminary findings that require replication in larger groups.

BiomarkersCognitive ImpairmentLong COVID Overlap

E2 ModerateCohortPEM unclearObservational

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study.

Kim, Laura, Cammà, Guido, Peters, Claudia Kedor et al.·Journal of translational medicine·2026

This observational study of 30 ME/CFS patients reported improvements in physical functioning, fatigue, and pain after 40 sessions of hyperbaric oxygen therapy (HBOT), with associated changes in brain connectivity patterns. However, this is a single-group study without a control arm receiving a sham or alternative treatment, so we cannot yet determine whether observed improvements were due to HBOT itself or other factors such as expectancy or natural variation.

NeuroinflammationInterventionsAutonomic Nervous SystemCognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Inderyas, Maira et al.·Frontiers in neuroscience·2026

Researchers used a brain imaging technique called DTI-ALPS to measure how well the brain clears waste during sleep in 31 ME/CFS patients and 27 healthy controls. They observed that ME/CFS patients had lower measurements than controls, and these measurements were associated with worse sleep disturbance and concentration problems. However, this is a preliminary study in a small group, and it remains unclear whether reduced glymphatic function actually causes ME/CFS symptoms or is simply correlated with them.

NeuroinflammationBiomarkersSleepCognitive Impairment

E2 ModerateCohortPEM unclearLongitudinal

Validation of the Wood Mental Fatigue Inventory in adolescents with myalgic encephalomyelitis/chronic fatigue syndrome.

Welch, David C, Edwards, Charles C, Broussard, Camille A et al.·Brain, behavior, & immunity - health·2026

This study tested whether a questionnaire called the Wood Mental Fatigue Inventory (WMFI) works well for measuring brain fog and cognitive problems in teenagers with ME/CFS. Researchers compared it to another commonly used teen fatigue scale and found that both questionnaires measured mental fatigue similarly and could track changes over time as teenagers received treatment.

Cognitive Impairment

E2 ModerateCohortPEM not requiredLongitudinal

Long COVID longitudinal symptoms burden clusters within a national community-based cohort.

Shen, Yanhan, Shahn, Zach, Robertson, McKaylee M et al.·BMC infectious diseases·2026

This study followed over 500 people with long COVID for up to a year, tracking their symptoms over time. Researchers identified three groups based on symptom burden: one with persistent severe symptoms (including fatigue, brain fog, post-exertional malaise, and pain), one with moderate symptoms that improved, and one with minimal symptoms. The findings are preliminary and based on self-reported data, so the stability and generalisability of these groups to other long COVID populations remain to be confirmed.

Pain and SensitizationSleepAutonomic Nervous SystemCognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.

Aregawi, Lillian, Walitt, Brian, Sullivan, Patti et al.·Brain communications·2026

Researchers measured levels of norepinephrine (a brain chemical) in cerebrospinal fluid from people with ME/CFS, Long COVID, and Parkinson's disease, comparing them to healthy volunteers. They observed that norepinephrine pathway activity was lower in all three patient groups, and in Long COVID patients with post-exertional malaise, this reduction was particularly pronounced. This is one study in a small sample, and it remains unclear whether these findings fully explain fatigue and brain fog or apply directly to ME/CFS.

BiomarkersCognitive ImpairmentLong COVID OverlapPost-Exertional Malaise

E2 ModeratePEM unclearRegistry-Resource

Risk factors for severe post-COVID condition in children, adolescents, and young adults.

Donath, Quirin, Haegele, Matthias, Schindler, Daniela et al.·European journal of pediatrics·2026

This observational study from a German pediatric hospital followed 120 children and young adults with post-COVID condition (PCC), observing that those with more severe illness were more likely to have had 12 or more symptoms during their initial COVID-19 infection, alongside other acute symptoms such as trouble concentrating and fainting-like episodes. One quarter of participants met criteria for ME/CFS, and all of these were in the severely affected group; by analogy, if similar patterns apply to ME/CFS patients, early identification of high-symptom-burden acute illness might help predict who develops severe long-term illness. These findings are preliminary and come from a single hospital site.

Severe MEAutonomic Nervous SystemDiagnosticsCognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Involvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndrome.

Azcue, N, Prada, A, Del Pino, R et al.·Scientific reports·2026

Researchers compared immune markers called autoantibodies in people with post-COVID condition, ME/CFS, and healthy controls. They found that people with ME/CFS had higher levels of antibodies against certain nerve receptors (β2 adrenergic), and these antibodies were associated with autonomic nervous system problems and memory changes. However, this is a single cross-sectional study, and autoimmunity remains one of several proposed mechanisms—it is not yet clear whether these antibodies are a cause or a consequence of ME/CFS.

BiomarkersAutonomic Nervous SystemImmune SystemCognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Identifying EEG biomarkers of fatigue and brain fog in long COVID: insights from rest and movement-related brain activity.

Casado Sánchez, M, Morales Fajardo, K, Long, S et al.·Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia·2026

A small study measured brain electrical activity in 20 people with long COVID who reported fatigue and brain fog, compared to 20 healthy controls. Researchers observed two types of altered brain patterns in the long COVID group: weaker electrical responses after hand movements and slower brain waves at rest in motor and sensory regions. These patterns were associated with cognitive symptoms and fatigue, but it remains unclear whether these brain changes explain the symptoms or are simply observed alongside them.

BiomarkersCognitive Impairment

E2 ModerateCohortPEM unclearObservational

Haptoglobin Phenotypes Stratify Post-Exertional Cognitive Dysfunction Associated with Altered Cerebral Oxygenation and Metabolic Signatures in Long COVID.

Moezzi, Atefeh, Elremaly, Wesam, Leveau, Corinne et al.·International journal of molecular sciences·2026

This study observed that Long COVID patients with different versions of a protein called haptoglobin showed different patterns of cognitive problems after physical exertion. Patients carrying certain haptoglobin variants (Hp2) reported worse fatigue and cognitive decline following a challenge test, while those with the Hp1-1 variant showed better cognitive resilience. The findings are preliminary and come from a small group; larger studies are needed to confirm whether haptoglobin type could help identify which Long COVID patients are at higher risk for these cognitive changes.

BiomarkersEnergy MetabolismCognitive ImpairmentLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

3D Virtual Reality Performance Metrics as a Future Fatigue Biomarker in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Ladek, Anja-Maria, Priebe, Leonie, Harrer, Thomas et al.·Biomedicines·2026

Researchers tested how quickly 60 ME/CFS patients and 60 healthy controls could react to visual tasks presented in 3D virtual reality. ME/CFS patients showed slower reaction times across all difficulty levels, and they improved less with practice than controls did. The study reports an association between ME/CFS and prolonged reaction times, though the findings are preliminary and whether this could become a reliable test for fatigue severity requires further validation.

BiomarkersDiagnosticsCognitive Impairment

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Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: a randomized, double-blind, placebo-controlled, crossover study.

Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal.

An assessment of cognitive function and mood in chronic fatigue syndrome.

Item comprehension and content coverage of patient-reported outcome measures for long COVID: a qualitative study.

Two-timepoint multidomain follow-up of post-COVID condition and ME/CFS: overlapping autonomic, small-fiber, and cognitive changes.

Symptom profiles and health-related quality of life in Korean adults with post-acute sequelae of SARS-CoV-2 infection (PASC): A latent profile analysis.

Disentangling comorbidity: symptom dimensions of internalizing and functional disorders in a large general population sample.

Assessment of dynamic cerebral blood flow changes during cognitive tasks in patients with post-COVID-19 syndrome.

Symptom, Functional, and Work Participation Profiles Among Racialized Canadians with Pre-Existing Mental Health Challenges and Long COVID: A Cross-Sectional Study.

Microstructural alterations in brain tissue of ME/CFS and long COVID using diffusion tensor imaging and diffusion kurtosis imaging.

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study.

Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.

Validation of the Wood Mental Fatigue Inventory in adolescents with myalgic encephalomyelitis/chronic fatigue syndrome.

Long COVID longitudinal symptoms burden clusters within a national community-based cohort.

Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.

Risk factors for severe post-COVID condition in children, adolescents, and young adults.

Involvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndrome.

Identifying EEG biomarkers of fatigue and brain fog in long COVID: insights from rest and movement-related brain activity.

Haptoglobin Phenotypes Stratify Post-Exertional Cognitive Dysfunction Associated with Altered Cerebral Oxygenation and Metabolic Signatures in Long COVID.

3D Virtual Reality Performance Metrics as a Future Fatigue Biomarker in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

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