ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

141–160 of 742 studies

E2 ModerateDiagnosticPEM unclearMethods-Paper

Agreement and reliability between the two-day 6-minute incremental step test and two-day cardiopulmonary exercise test in post COVID-19 condition for assessing post-exertional malaise: The REVEAL-study.

Bomans, Sarah, Michotte, Naomi, El M'Rabet, Imane et al.·PloS one·2026

Researchers compared two different exercise tests—one simpler and potentially more accessible (the 6-minute incremental step test) and one more complex (the cardiopulmonary exercise test)—to see if they could both measure post-exertional malaise in long COVID patients. In a small study of 25 people, the two tests did not measure the same outcomes equally well, though some measures like fatigue and effort perception showed moderate agreement. The simpler test may need further refinement before it can reliably replace the standard test.

DiagnosticsPost-Exertional Malaise

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 ModerateCohortPEM requiredObservational

Assessment and Incidence Determination of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Following a SARS-CoV-2 Infection in a Prospective Cohort of Hospital Employees.

Tack, Matthias, Gruber, Rosalie, Betting, Leia et al.·Medicina (Kaunas, Lithuania)·2026

This study followed hospital workers who got COVID-19 to see how many developed long-lasting fatigue and ME/CFS. About 12% still had fatigue months later, and 3% met the criteria for ME/CFS. Researchers found that people with these conditions often had signs of viral reactivation, immune system changes, and blood clotting abnormalities.

Post-Exertional Malaise

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

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

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 unclearLongitudinal

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

Jones, Ansley E, Khan, Zain, McGroder, Claire F et al.·Critical care explorations·2026

This study followed people who were hospitalized with severe COVID-19 for 3 years after they left the hospital. About one-quarter of them continued to experience long COVID symptoms like fatigue, brain fog, and difficulty with physical activity. Surprisingly, when researchers measured inflammation and blood vessel markers in their blood, these markers were not elevated and did not explain why some people had ongoing symptoms.

BiomarkersImmune SystemPost-Exertional Malaise

E2 ModerateCohortPEM requiredCross-Sectional

Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study.

Inderyas, Maira, Thapaliya, Kiran, Marshall-Gradisnik, Sonya et al.·Journal of translational medicine·2026

This study used advanced brain imaging to compare how the brains of ME/CFS patients, long COVID patients, and healthy people work during a challenging thinking task. Researchers found that patients' brains show different patterns of communication between regions compared to healthy controls, particularly in areas related to motivation, memory, and emotional processing. These brain differences appeared to worsen as fatigue built up during the task.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

Wearable Heart Rate Variability Monitoring, Autonomic Dysfunction and Post-exertional Malaise in Long COVID: An Observational Study.

Ruijgt, Twan M, Slaghekke, Anouk, Ellens, Anneke et al.·Sports medicine (Auckland, N.Z.)·2026

This observational study measured heart rate variability (a marker of nerve system balance) in 121 long COVID patients and 21 healthy controls using wearable devices over multiple days. Researchers observed that long COVID patients had lower heart rate variability during daily activities and sleep, and their heart rate variability remained reduced for 24 hours after exercise, particularly at intensities above their aerobic threshold. The findings suggest wearables may help patients recognise when they are overexerting, though the study does not yet establish whether this monitoring prevents post-exertional malaise.

BiomarkersAutonomic Nervous SystemDiagnosticsPost-Exertional Malaise

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 requiredCross-Sectional

Identifying post-exertional malaise subtypes: Differentiating physical and mental PEM manifestations.

Tuzzolino, Katherine, Jason, Leonard A, Furst, Jacob·Journal of health psychology·2026

This study looked at how post-exertional malaise (PEM)—the worsening of symptoms after activity—shows up differently in people with ME/CFS. Researchers divided patients into groups based on whether their PEM affected them physically (like muscle pain), mentally (like brain fog), both ways, or neither way severely. They found that people experiencing both physical and mental PEM had the worst overall symptoms, while those with neither type of severe PEM were less affected, though still much more disabled than healthy people.

Post-Exertional Malaise

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 not requiredObservational

Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases.

Ghali, Alaa, Lavigne, Christian, Ghali, Maria et al.·Journal of clinical medicine·2026

A French hospital study observed that post-COVID patients infected in 2020–2021 reported post-exertional malaise (PEM) more often than those infected later, and that PEM was associated with higher fatigue levels. By analogy, this may be relevant to ME/CFS patients, though the study examined post-COVID populations and the reasons for these differences remain uncertain—they could reflect changes in the virus, vaccination, immunity, or other unmeasured factors.

Long COVID OverlapPost-Exertional Malaise

E2 ModerateCohortPEM requiredCross-Sectional

Impact of post-exertional malaise frequency and fatigue in Long COVID patients on health-related quality of life.

Thölking, Theresa, Müller, Frank, Riester, Tim et al.·Health and quality of life outcomes·2026

This study surveyed German adults with Long COVID and post-exertional malaise (PEM) to understand how the frequency and severity of PEM relates to quality of life. Researchers found that people reporting more frequent and more severe PEM were associated with lower quality-of-life scores, even after accounting for age, sex, and employment status. These are preliminary findings from a single survey and do not establish that PEM causes poor quality of life, but rather that the two observations occurred together in this group.

Post-Exertional Malaise

E2 ModerateCohortPEM requiredObservational

Handgrip strength in children, adolescents, and young adults with suspected myalgic encephalomyelitis/chronic fatigue syndrome.

Mihatsch, Lorenz, Schartner, Lisa, de Luna, Julia Lange et al.·Journal of translational medicine·2026

Researchers tested whether handgrip strength could help identify ME/CFS in young people (ages 10–25). They asked 147 patients referred for ME/CFS assessment and 83 healthy controls to squeeze a hand-strength device twice, an hour apart. Young people with ME/CFS had weaker grip strength than healthy controls, and grip strength was loosely associated with physical functioning; however, grip strength alone could not reliably tell apart ME/CFS patients from other young people with chronic fatigue. The study shows that repeated handgrip testing is feasible and may help track how patients are doing over time, but early findings suggest it works better as a way to measure general weakness rather than as a standalone diagnostic test.

BiomarkersDiagnosticsPost-Exertional Malaise

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 unclearCase-Control

Interpreting hand grip strength in hospital employees with post-COVID syndrome compared to non-infected controls: a case-control study.

Tack, Matthias, Gruber, Rosalie, Betting, Leia et al.·Scientific reports·2026

This small study compared hand grip strength in 19 hospital workers with post-COVID syndrome (including 7 who met ME/CFS criteria) to 23 healthy controls. Researchers found that grip strength tended to be lower in the post-COVID group, particularly when tested a second time after a 60-minute break, which might suggest difficulty recovering after repeated effort. However, these are preliminary findings from a small group, and the authors note that grip strength alone is not reliable enough to diagnose post-COVID syndrome.

DiagnosticsPost-Exertional Malaise

E2 ModerateCohortPEM unclearLongitudinal

Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID.

Polli, Andrea, Godderis, Lode, Martens, Dries S et al.·BMC medicine·2025

This study followed 358 people who had COVID-19 to understand why some develop Long-COVID with symptoms like extreme fatigue, sleep problems, and post-exertional malaise (feeling much worse after activity). Researchers measured biological markers in blood and found that two factors—elevated troponin T (a heart protein) and shortened telomeres (the protective caps on DNA)—were most strongly linked to Long-COVID, particularly the fatigue cluster. The study shows that Long-COVID is not a single illness but has different symptom patterns, suggesting different underlying causes may be at play.

BiomarkersPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Health outcomes one year after Omicron infection among 12,789 adults: a community-based cross-sectional study.

Zhang, Hui, Yang, Peng, Gu, Xiaoying et al.·The Lancet regional health. Western Pacific·2025

This study followed over 12,000 people in Beijing who had COVID-19 (Omicron variant) about one year earlier. Researchers found that roughly 8% still had long COVID symptoms, with fatigue and post-exertional malaise (feeling worse after activity) being the most common complaints. People who had been reinfected with COVID were at much higher risk of developing long COVID.

Post-Exertional Malaise

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Evidence Atlas

Evidence browser

Agreement and reliability between the two-day 6-minute incremental step test and two-day cardiopulmonary exercise test in post COVID-19 condition for assessing post-exertional malaise: The REVEAL-study.

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.

Assessment and Incidence Determination of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Following a SARS-CoV-2 Infection in a Prospective Cohort of Hospital Employees.

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

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

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

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study.

Wearable Heart Rate Variability Monitoring, Autonomic Dysfunction and Post-exertional Malaise in Long COVID: An Observational Study.

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

Identifying post-exertional malaise subtypes: Differentiating physical and mental PEM manifestations.

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

Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases.

Impact of post-exertional malaise frequency and fatigue in Long COVID patients on health-related quality of life.

Handgrip strength in children, adolescents, and young adults with suspected myalgic encephalomyelitis/chronic fatigue syndrome.

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.

Interpreting hand grip strength in hospital employees with post-COVID syndrome compared to non-infected controls: a case-control study.

Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID.

Health outcomes one year after Omicron infection among 12,789 adults: a community-based cross-sectional study.

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