Evidence browser

Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome.

Haunhorst, Simon, Dudziak, Diana, Scheibenbogen, Carmen et al.·Infection·2025

This review examines why people with ME/CFS and long COVID feel much worse after physical activity—a condition called post-exertional malaise. The researchers found that when these patients exercise, their bodies struggle to use oxygen properly and produce energy efficiently, likely due to problems with tiny blood vessels and lingering immune activation. This causes a buildup of harmful substances like lactate and triggers further inflammation and exhaustion.

Assessment of symptoms in myalgic encephalomyelitis/chronic fatigue syndrome: a comparative study of existing scales.

Lu, Jing, Sun, Weibo, Li, Shulin et al.·Frontiers in neurology·2025

This review examined the different questionnaires and tests doctors use to measure ME/CFS symptoms. The researchers looked at how well these tools work for diagnosing the illness and tracking how patients change over time. They found that while current tests are reasonably reliable, we need better tools that measure all the different ways ME/CFS affects people—like fatigue, brain fog, pain, and sleep problems—in a more consistent and objective way.

The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology.

Clarke, Krista S P, Kingdon, Caroline C, Hughes, Michael Pycraft et al.·Journal of translational medicine·2025

This review looked at recent research on finding a simple blood test that could definitively diagnose ME/CFS, which currently takes years and relies on ruling out other diseases. Scientists have found several promising approaches—including measuring immune cell properties, checking how blood cells respond to stress, and detecting metabolic changes—that show they can tell ME/CFS patients apart from healthy people and others with different illnesses. However, these tests need more testing in larger groups and practical refinement before doctors can use them in everyday care.

E0 ConsensusReviewPEM unclearEvidence-Map

Recent research in myalgic encephalomyelitis/chronic fatigue syndrome: an evidence map.

Todhunter-Brown, Alex, Campbell, Pauline, Broderick, Cathryn et al.·Health technology assessment (Winchester, England)·2025

This study looked at all ME/CFS research published between 2018 and 2023 to see what scientists have been studying and how much research exists on different topics. Researchers found 639 studies involving over 600,000 people with ME/CFS. More than half of the research focused on trying to understand what causes ME/CFS, while fewer studies looked at treatments or how to diagnose the condition. The researchers created an interactive map so patients and doctors can explore what research has been done.

COVID-19-associated neurological and psychological manifestations.

Wilson, Jo Ellen, Gurdasani, Deepti, Helbok, Raimund et al.·Nature reviews. Disease primers·2025

Long COVID is a condition that develops after COVID-19 infection and causes ongoing symptoms for at least 3 months. People with Long COVID commonly experience brain fog, memory problems, anxiety, depression, headaches, sleep issues, and severe exhaustion after physical activity. This review explains what we know about what causes these symptoms and why treatment needs to be personalized based on each person's unique symptoms.

E0 ConsensusReviewPEM unclearMeta-Analysis

Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis.

Hendrix, Jolien, Fanning, Lara, Wyns, Arne et al.·European journal of clinical investigation·2025

Researchers analyzed 37 studies comparing how the bodies of ME/CFS and fibromyalgia patients handle stress hormones compared to healthy people. They found that ME/CFS patients have higher levels of adrenaline at rest and unusual responses to exercise and position changes—suggesting their nervous system doesn't regulate stress hormones normally. These findings point to a specific biological problem in ME/CFS that might be treatable.

NeuroinflammationBiomarkersPost-Exertional Malaise

Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID.

Zhu, Yijuan, Quan, Patrick, Yamazaki, Tadahiro et al.·Immunometabolism (Cobham, Surrey)·2025

This review examines brain imaging studies that look at how the brains of people with ME/CFS and Long-COVID process energy and nutrients differently. Researchers used advanced scanning techniques to measure glucose and oxygen use in the brain, finding that both conditions show similar patterns of disrupted brain energy metabolism and inflammation. The findings suggest these brain changes might explain why patients experience persistent fatigue, thinking problems, and worsening after physical activity.

BiomarkersImmune SystemCognitive ImpairmentPost-Exertional Malaise

Chronic Fatigue Syndrome: Diagnosis, Treatment, and Future Direction.

Graves, B Sue, Patel, Mitsu, Newgent, Hailey et al.·Cureus·2024

ME/CFS is a serious illness that causes extreme tiredness that doesn't improve with rest and often gets worse with activity. People with ME/CFS also struggle with brain fog, pain, sleep problems, and immune system issues. Right now, doctors don't have a simple blood test or scan to diagnose ME/CFS, which makes it hard to identify and treat the condition properly.

Prevalence and measurement of post-exertional malaise in post-acute COVID-19 syndrome: A systematic review and meta-analysis.

An, Yi, Guo, Ziyu, Fan, Jin et al.·General hospital psychiatry·2024

Researchers looked at 12 studies involving 2,665 patients with long COVID to understand how common post-exertional malaise (PEM)—a worsening of symptoms after physical or mental effort—is among those affected. They found that more than half of long COVID patients experience PEM. The study also identified seven different questionnaires that researchers use to measure PEM, with the DePaul Symptom Questionnaire being the most commonly used tool.

Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses.

Apostolou, Eirini, Rosén, Anders·Journal of internal medicine·2024

This review examines how viruses, particularly Epstein-Barr virus, may cause lasting changes to how our cells work in ME/CFS patients. The authors found that in about 70% of ME/CFS cases, the illness begins after a viral infection, and viruses can hide in the body while triggering long-term problems with energy, thinking, and immune function. Understanding these viral-triggered changes could help explain why different patients experience ME/CFS differently and may lead to better treatments.

Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives.

Seton, Katharine A, Espejo-Oltra, José A, Giménez-Orenga, Karen et al.·Journal of clinical medicine·2024

This review examined research studies testing various treatments for ME/CFS, including medications and supplements that target different aspects of the illness like immune function, metabolism, and gut health. The authors found that current treatments mainly manage symptoms rather than address the root causes, with very few patients recovering fully. They emphasize that better-designed clinical trials are urgently needed to find treatments that actually work and can be used in real-world medical practice.

E0 ConsensusReviewPEM not requiredMeta-Analysis

Does the effect of cognitive behavior therapy for chronic fatigue syndrome (ME/CFS) vary by patient characteristics? A systematic review and individual patient data meta-analysis.

Kuut, T A, Buffart, L M, Braamse, A M J et al.·Psychological medicine·2024

This study combined data from 8 clinical trials involving 1,298 people with ME/CFS to see whether cognitive behavior therapy (CBT) works and who benefits most from it. Researchers found that CBT did help reduce fatigue, improve daily functioning, and increase physical activity—but the amount of benefit varied depending on patient characteristics like age, how much disability someone had, and their activity patterns. Younger patients, those with less severe disability at the start, and those with fluctuating activity patterns saw the most improvement.

Severe MEPost-Exertional Malaise

Severe MESleepPost-Exertional Malaise

The persistence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis.

Dehlia, Ankush, Guthridge, Mark A·The Journal of infection·2024

Researchers looked at studies of people with Long COVID to see how many also meet the diagnostic criteria for ME/CFS. They found that about half of Long COVID patients have symptoms that match ME/CFS, including severe fatigue, sleep problems, muscle and joint pain, and post-exertional malaise (feeling much worse after physical activity). This suggests that Long COVID and ME/CFS may be very similar conditions, at least in some patients.

Long COVID in pediatrics-epidemiology, diagnosis, and management.

Toepfner, Nicole, Brinkmann, Folke, Augustin, Silvia et al.·European journal of pediatrics·2024

This review looked at what we know about Long COVID in children and teenagers after COVID-19 infection. Most young people recover within a few months, but some experience long-lasting symptoms like fatigue, difficulty with exercise, and anxiety that can last over a year and affect daily life. The review found that a small number of these children meet the criteria for ME/CFS, but currently there are no blood tests or scans to confirm Long COVID, making it difficult to diagnose.

Qigong and Tai Chi for ME/CFS: A Systematic Review of Randomized Controlled Trials.

Markwart, Michaela, Felsenstein, Donna, Mehta, Darshan H et al.·Global advances in integrative medicine and health·2024

This review looked at studies testing whether Qigong (a gentle Chinese exercise practice) might help people with ME/CFS. Researchers found 5 good-quality studies with a total of 481 people. The results suggest Qigong may help reduce symptom severity and improve both physical and emotional well-being, though more research is needed to be sure. Currently, there are no similar high-quality studies on Tai Chi for ME/CFS.

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview.

Mantle, David, Hargreaves, Iain Parry, Domingo, Joan Carles et al.·International journal of molecular sciences·2024

This review examines whether problems with mitochondria—the energy-producing structures inside our cells—contribute to post-viral fatigue conditions like ME/CFS, long COVID, and fibromyalgia. The researchers looked at existing research to see if a supplement called Coenzyme Q10 might help reduce fatigue and pain by supporting mitochondrial function. While mitochondrial dysfunction appears linked to these conditions, more research is needed to confirm whether CoQ10 supplementation is an effective treatment.

E0 ConsensusReviewPEM not requiredReview-Narrative

Long COVID: Long-Term Impact of SARS-CoV2.

Makhluf, Huda, Madany, Henry, Kim, Kenneth·Diagnostics (Basel, Switzerland)·2024

Long COVID is a condition affecting millions of people worldwide who continue to experience health problems months or years after a SARS-CoV-2 infection. This review article examines what we know about Long COVID symptoms—including severe tiredness, difficulty thinking clearly, heart problems, and sleep issues—and explains current theories about why these symptoms develop. The authors also summarize available treatments and clinical trials testing new approaches to help people recover.

Translating insights into therapies for Long Covid.

Antar, Annukka A R, Cox, Andrea L·Science translational medicine·2024

Long Covid causes a variety of symptoms—like exhaustion, weakness, and brain fog—that last long after a COVID-19 infection ends. This review examines what scientists currently understand about what might cause Long Covid and looks at early laboratory studies and clinical trials testing potential treatments. The authors emphasize that more large-scale research is needed to understand why different people experience different symptoms and to develop effective therapies.

E0 ConsensusReviewPEM not requiredReview-Narrative

Long COVID: lights and shadows on the clinical characterization of this emerging pathology.

Cogliandro, Viola, Bonfanti, Paolo·The new microbiologica·2024

This review examined Long COVID, a condition affecting 10-20% of people who had COVID-19 infection. Long COVID causes multiple symptoms across different body systems that significantly reduce quality of life. The review highlights that some Long COVID patients develop conditions like POTS (a heart rhythm problem when standing), ME/CFS (severe fatigue and post-exertional symptoms), and brain fog, and summarizes what treatments might help.

Long COVID OverlapPost-Exertional Malaise

Physical Activity and Fatigue Symptoms: Neurotypical Adults and People with Chronic Multisymptom Illnesses.

Boruch, Alex, Branchaw, Grace, O'Connor, Patrick J et al.·Current topics in behavioral neurosciences·2024

This review examined how physical activity affects fatigue in people with ME/CFS and similar long-term illnesses, compared to healthy people. In healthy adults, exercise usually makes people feel more energized, but in people with ME/CFS and related conditions, exercise often makes fatigue worse. Short-term exercise programs show small improvements in fatigue for healthy people, but little to no improvement for those with these chronic illnesses.