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Immune SystemCognitive ImpairmentPost-Exertional Malaise

Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Ivanovska, Mariya, Homadi, Maysam Salim, Angelova, Gergana et al.·Biomedicines·2025

This review compared Long-COVID (illness after COVID-19) and ME/CFS (chronic fatigue syndrome), which share similar symptoms like extreme tiredness, difficulty thinking clearly, and problems with the nervous system. While both conditions likely involve immune system problems, viral persistence, and blood vessel issues, they appear to have some differences in how they develop. Currently, there is no cure for either condition, though lifestyle management and rehabilitation help some people.

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.

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.

NeuroinflammationImmune SystemPost-Exertional Malaise

Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.

Takamatsu, Naoki, Kuga, Hironori·BMC infectious diseases·2025

This review examined whether cognitive behavior therapy (CBT)—a talking therapy that helps address thought patterns and behaviors—might help patients with long COVID who experience brain fog, fatigue, and mood problems. The authors compared long COVID to ME/CFS, noting they share many features, and found that while CBT may help some patients feel less tired and think more clearly, it works best when tailored to each person's energy limits and combined with other treatments. Importantly, the authors stress that suggesting CBT does not mean these illnesses are 'all in your head'—they have real physical causes.

Gut MicrobiomeImmune SystemPost-Exertional Malaise

Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Insights into Disease Mechanisms.

Nikolova, Ralitsa, Donchev, Deyan, Vaseva, Katya et al.·International journal of molecular sciences·2025

This review examines the connection between gut bacteria and ME/CFS, a condition characterized by exhaustion that worsens after activity. The authors explain how an imbalance in gut bacteria may damage the intestinal barrier, allowing bacterial particles to enter the bloodstream and trigger inflammation throughout the body. They also discuss how changes in gut bacteria might affect the brain, contributing to the brain fog and cognitive problems many ME/CFS patients experience.

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.

BiomarkersPost-Exertional Malaise

Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia.

Davis, Leah, Higgs, Maisy, Snaith, Ailsa et al.·Frontiers in neuroscience·2025

This review examined research showing that ME/CFS, Gulf War Syndrome, and fibromyalgia may share similar problems with how the body produces energy and handles stress at the cellular level. Scientists found that these three conditions show signs of disrupted fat metabolism, energy production difficulties, and increased cellular damage from oxidative stress. Better understanding these shared biological problems could help doctors diagnose these conditions faster and develop treatments that target the root causes rather than just treating symptoms.

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.

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.

Postacute Sequelae of SARS-CoV-2 in Children.

Rao, Suchitra, Gross, Rachel S, Mohandas, Sindhu et al.·Pediatrics·2024

Some children who have COVID-19 experience symptoms that last for weeks or months after the initial infection—a condition called long COVID. This review summarizes what we currently know about long COVID in children, including how common it is, what symptoms children experience, and what might cause it. The authors also describe major research efforts being funded to better understand long COVID in young people and find effective 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.

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.

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.

The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives.

Stallmach, Andreas, Quickert, Stefanie, Puta, Christian et al.·Frontiers in immunology·2024

This review examines whether changes in gut bacteria might play a role in ME/CFS, particularly in cases that develop after infections like COVID-19. The authors found that many ME/CFS patients do show differences in their gut bacteria compared to healthy people, and these changes might trigger immune and inflammatory problems. However, the review concludes that current research hasn't proven that gut bacteria changes actually cause ME/CFS—only that they often occur together.

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.

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.

Developing effective strategies to optimize physical activity and cardiorespiratory fitness in the long Covid population- The need for caution and objective assessment.

Faghy, Mark A, Duncan, Rae, Hume, Emily et al.·Progress in cardiovascular diseases·2024

Long Covid affects millions of people worldwide with over 200 recognized symptoms that severely impact daily life. A key feature is post-exertional malaise (PEM)—a condition where symptoms dramatically worsen 24-72 hours after physical, mental, or emotional activity, sometimes lasting weeks. This review examines how to safely design rehabilitation programs for Long Covid patients while using objective monitoring tools to track how individuals respond to different activities and prevent symptom flare-ups.

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.

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.

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.