ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

1021–1040 of 6,157 studies

E2 ModerateCohortPEM not requiredCross-Sectional

Clinical Importance of Central Sensitization and Neuropathic Pain in The Treatment and Follow-Up of Patients with Psoriasis and Psoriatic Arthritis.

Koca, Tuba Tülay, Göğebakan, Hasan, Nazik, Hülya et al.·Indian journal of dermatology·2026

This study looked at whether people with skin and joint conditions (psoriasis and psoriatic arthritis) experience unusual pain processing in their nervous system, similar to what happens in conditions like fibromyalgia. Researchers found that many patients with these conditions had signs of nervous system sensitization and neuropathic pain (nerve-related pain). The more active their disease was, the more likely they were to have these pain processing problems.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCross-Sectional

Subclinical Hypercoagulable Viscoelastic Characteristics Associated with Post-Acute Sequelae of SARS-CoV2 Physical Symptoms in COVID-19 ALI/ARDS Survivors.

Jones, Ansley E, Mira-Sanchez, Margarita, Khan, Zain et al.·Journal of intensive care medicine·2026

This study examined blood clotting patterns in 93 people who survived severe COVID-19 requiring hospitalization, testing them 15 months after discharge. Researchers observed that those with lingering post-COVID symptoms—particularly fatigue and post-exertional malaise (worsening after activity)—showed altered clotting characteristics on specialized blood tests, specifically higher fibrinogen levels. However, this is a single cross-sectional study and does not establish whether these clotting changes cause the symptoms or are simply associated with them.

BiomarkersLong COVID Overlap

E2 ModerateCohortPEM requiredObservational

[The Role of ME/CFS Phenotype in Outpatient Post-COVID Rehabilitation].

Kaiserseder, Moritz, Prüfer, Ferdinand, Untersmayer-Elsenhuber, Eva et al.·Pneumologie (Stuttgart, Germany)·2026

This study looked at 216 people recovering from COVID-19 in rehabilitation programs to see how many had ME/CFS—a condition with severe fatigue and worsening after physical activity. The researchers found that about 7% of these patients met the criteria for ME/CFS. These patients were typically younger, mostly women, and experienced much more severe fatigue that didn't improve with rehabilitation compared to other COVID-19 patients.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID.

Petrov, Steliyan, Bozhkova, Martina, Ivanovska, Mariya et al.·International journal of molecular sciences·2026

Researchers compared immune cell patterns in 103 people with ME/CFS, 63 with long COVID, and 41 healthy controls using blood tests. They observed that ME/CFS and long COVID show different patterns of immune cell activity—long COVID appeared to show persistent immune activation, while ME/CFS appeared associated with reduced immune signalling. These are early findings from one study and do not yet tell us what causes either condition or how to treat it.

BiomarkersDiagnosticsImmune SystemLong COVID Overlap

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 ModerateCohortPEM unclearCross-Sectional

Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation.

Grach, Stephanie L, Seltzer, Jaime, Mueller, Michael R et al.·Annals of family medicine·2026

A study of 571 ME/CFS patients in Minnesota found that about two-thirds had tried at least one medication before seeing a specialist, and over 70% had used dietary supplements. The researchers observed that medications commonly recommended by ME/CFS specialists—such as certain antidepressants and gabapentin—appear to be prescribed less often by general doctors compared to pain and anxiety medications. It remains unclear whether this pattern reflects clinical caution, lack of awareness, or other factors in primary care practice.

Interventions

E2 ModerateCohortPEM unclearObservational

Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome.

Mancini, Donna M, Cook, Dane B, Brunjes, Danielle L et al.·Frontiers in physiology·2026

Researchers asked whether doing two exercise tests on consecutive days could reliably detect post-exertional malaise (PEM) in ME/CFS patients. They found that oxygen consumption and other key exercise measures did not change between Day 1 and Day 2 in either ME/CFS patients or healthy controls. However, ME/CFS patients reported much greater fatigue during exercise and had lower maximum heart rates. One study's findings do not establish whether this two-day test method is truly useful for measuring PEM in clinical practice.

DiagnosticsPost-Exertional Malaise

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

Raman Spectroscopy Combined with Machine Learning Reveals Myalgic Encephalomyelitis-Associated Biomolecular Signatures at Rest and After Standardized Stress.

Heidarifard, Maryam, Moezzi, Atefeh, Dallaire, Frédérick et al.·International journal of molecular sciences·2026

Researchers used a laboratory technique called Raman spectroscopy combined with computer learning to identify chemical signatures in blood plasma that are associated with ME/CFS. They collected blood samples from 115 ME/CFS patients and 45 healthy controls both at rest and 90 minutes after a standardized stress test, and found the method could distinguish between the two groups with moderate-to-good accuracy (79–84%). However, this is an early-stage study and much more work is needed before such a test could be used in clinical practice.

BiomarkersDiagnosticsPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.

Souma, Bernard, Elremaly, Wesam, Akoume, Marie-Yvonne et al.·International journal of molecular sciences·2026

Researchers compared blood levels of two proteins—irisin and thrombospondin-1 (TSP-1)—in 92 ME/CFS patients and 44 healthy controls, measuring them before and after a physical stress test. They observed that ME/CFS patients had lower baseline irisin levels and a weaker response to the stress challenge, while those with more severe symptoms showed elevated levels of both proteins. The study proposes that TSP-1 may interfere with irisin's normal signaling, potentially contributing to energy problems in ME/CFS, but these findings are preliminary and require validation in larger studies.

BiomarkersEnergy MetabolismPost-Exertional Malaise

E2 ModerateCohortPEM unclearLongitudinal

Outcomes of ME/CFS following infectious mononucleosis: seven-year follow-up of a prospective study.

Jason, Leonard A, Furst, Jacob, Worth, Rebecca et al.·Frontiers in medicine·2026

This study followed college students over 7 years to see what happened to those who developed ME/CFS after infectious mononucleosis caused by Epstein-Barr virus (EBV). Researchers found that people who had severe ME/CFS 6 months after their infection were very likely to still have ME/CFS 7 years later, while those with milder symptoms often recovered. This suggests that how sick someone is early on may predict whether ME/CFS will persist long-term.

E2 ModerateCohortPEM unclearLongitudinal

Long COVID-19: a Four-Year prospective cohort study of risk factors, recovery, and quality of life.

Kamal, Sanaa M, Al Qahtani, Mohammed S, Al Aseeri, Ali et al.·BMC infectious diseases·2025

This study followed 816 people in Saudi Arabia for up to four years after they had COVID-19 to see who developed long COVID and what symptoms they experienced. Researchers found that about 29% developed long COVID, with fatigue, post-exertional malaise (worsening after activity), cough, and brain fog being the most common symptoms. Women and people with diabetes were at higher risk, and those who got reinfected or were hospitalized took longer to recover.

Post-Exertional Malaise

E2 ModerateBehavioralPEM not requiredCross-Sectional

Comparing autonomic nervous system function in patients with functional somatic syndromes, stress-related syndromes and healthy controls.

Van Den Houte, Maaike, Ramakers, Indra, Van Oudenhove, Lukas et al.·Journal of psychosomatic research·2025

This study measured how the nervous system responds to stress in people with ME/CFS and similar conditions, compared to healthy people. Researchers found that patients with ME/CFS and stress-related conditions had their 'stress response system' stuck in overdrive even at rest, and this system didn't properly calm down after stress passed. These findings suggest that autonomic nervous system dysfunction—an imbalance in the automatic systems that control heart rate and other vital functions—may be a common feature across these conditions.

Autonomic Nervous System

E2 ModerateCohortPEM unclearCross-Sectional

Distinct white matter alteration patterns in post-infectious and gradual onset chronic fatigue syndrome revealed by diffusion MRI.

Yu, Qiang, Kwiatek, Richard A, Del Fante, Peter et al.·Scientific reports·2025

This study used advanced brain imaging to examine whether two types of ME/CFS—one that starts suddenly after an infection and one that develops gradually—show different patterns of damage in the brain's white matter (the nerve fibers that allow brain regions to communicate). Researchers found that these two types of ME/CFS do indeed show distinct patterns, suggesting they may involve different disease processes. This finding supports the idea that ME/CFS is not a single uniform condition but may require different approaches depending on how it started.

E2 ModerateCohortPEM unclearObservational

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

E2 ModerateCohortPEM unclearObservational

Autonomic Dysfunction in Patients with Acute Infection with Coxiella burnetii.

Milovanović, Branislav, Marković, Nikola, Ristanović, Elizabeta et al.·Pathogens (Basel, Switzerland)·2025

This study looked at how the autonomic nervous system (the part that controls heart rate, blood pressure, and other automatic body functions) works in people who had acute infection with Coxiella burnetii, a bacterium that causes Q fever. Researchers tested 100 infected patients and 56 healthy controls using heart monitoring tests and found that infected patients had more problems with autonomic control, particularly in how their bodies regulate heart rate and blood pressure. These findings suggest that this infection might trigger lasting problems with the autonomic nervous system that could contribute to ME/CFS symptoms.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

The Relationship Between Hemodynamic Responses During Head-Up Tilt Testing and Parameters of Infection in Post-COVID Syndrome, Chronic Fatigue Syndrome, and Late-Stage Lyme Disease.

Milovanovic, Branislav, Markovic, Nikola, Petrovic, Masa et al.·Viruses·2025

This study examined 1036 patients with post-COVID syndrome, chronic fatigue syndrome, and Lyme disease to understand why they experience dizziness and fainting when standing up. Researchers performed tilt-table tests (where patients lie on a table that tilts upward) and checked for signs of past or ongoing infections through blood tests. They found that patients with evidence of multiple past infections were more likely to have abnormal responses during the tilt test, suggesting that lingering effects from infections may affect the nervous system's ability to control blood pressure and heart rate.

Autonomic Nervous System

E2 ModerateCohortPEM requiredObservational

Post-exertional malaise in Long COVID: subjective reporting versus objective assessment.

Stussman, Barbara, Camarillo, Nathan, McCrossin, Gayle et al.·Frontiers in neurology·2025

This study looked at post-exertional malaise (PEM)—the symptom worsening that happens after activity—in people with Long COVID. Researchers asked patients about PEM symptoms and had some patients do an exercise test to see if PEM actually occurred. While 67% of patients reported having PEM symptoms, only 6% actually showed clear PEM after the exercise test. When PEM did occur in Long COVID, it was less severe than what the researchers saw in ME/CFS patients.

Severe MEPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

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.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Long COVID in the population of COVID-19 hospitalized patients discharged from SUS' hospitals in Rio de Janeiro City, Brazil: a patient-engaged cohort survey study.

Portela, Margareth Crisóstomo, Lima, Sheyla Maria Lemos, Escosteguy, Claudia Caminha et al.·BMC infectious diseases·2025

This Brazilian study surveyed over 11,000 people who were hospitalized with COVID-19 to see how many experienced long-lasting symptoms months later. About 71% reported frequent ongoing symptoms like fatigue, brain fog, and joint pain, while 39% said they had Long COVID. The researchers found that women, people with previous health conditions, and certain age groups were more likely to experience these persistent symptoms.

Post-Exertional Malaise

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Clinical Importance of Central Sensitization and Neuropathic Pain in The Treatment and Follow-Up of Patients with Psoriasis and Psoriatic Arthritis.

Subclinical Hypercoagulable Viscoelastic Characteristics Associated with Post-Acute Sequelae of SARS-CoV2 Physical Symptoms in COVID-19 ALI/ARDS Survivors.

[The Role of ME/CFS Phenotype in Outpatient Post-COVID Rehabilitation].

Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID.

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

Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation.

Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome.

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

Raman Spectroscopy Combined with Machine Learning Reveals Myalgic Encephalomyelitis-Associated Biomolecular Signatures at Rest and After Standardized Stress.

Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.

Outcomes of ME/CFS following infectious mononucleosis: seven-year follow-up of a prospective study.

Long COVID-19: a Four-Year prospective cohort study of risk factors, recovery, and quality of life.

Comparing autonomic nervous system function in patients with functional somatic syndromes, stress-related syndromes and healthy controls.

Distinct white matter alteration patterns in post-infectious and gradual onset chronic fatigue syndrome revealed by diffusion MRI.

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

Autonomic Dysfunction in Patients with Acute Infection with Coxiella burnetii.

The Relationship Between Hemodynamic Responses During Head-Up Tilt Testing and Parameters of Infection in Post-COVID Syndrome, Chronic Fatigue Syndrome, and Late-Stage Lyme Disease.

Post-exertional malaise in Long COVID: subjective reporting versus objective assessment.

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

Long COVID in the population of COVID-19 hospitalized patients discharged from SUS' hospitals in Rio de Janeiro City, Brazil: a patient-engaged cohort survey study.

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