Evidence browser

DiagnosticsPost-Exertional Malaise

Quantifying the Degree of Fatigue in People Reporting Symptoms of Post-COVID-19 Syndrome: Results from a Rasch Analysis.

Mayo, Nancy, Brouillette, Marie-Josée, Fellows, Lesley K et al.·Physiotherapy Canada. Physiotherapie Canada·2025

Researchers in this study developed and tested a new questionnaire to measure fatigue severity in people with post-COVID-19 syndrome. The measure, called the PCS Fatigue Severity Measure V1, performed well in their analysis of 414 participants—it correlated strongly with other fatigue measures and distinguished between people still working and those on sick leave. However, this is early-stage research in a single Canadian cohort, and the authors note that further testing in other populations is needed to confirm the measure's reliability over time.

E2 ModerateBehavioralPEM not requiredCross-Sectional

Network structure of functional somatic symptoms.

Litzenburger, Alexandra, Rothacher, Yannick, Hanusch, Kay-Uwe et al.·Journal of psychosomatic research·2025

This study looked at how symptoms cluster together in people with functional somatic syndromes (like ME/CFS, fibromyalgia, and others). Researchers surveyed over 3,000 young adults and used network analysis to map which symptoms tend to appear together. They found that fatigue and depression are particularly important symptoms that connect different symptom groups, and identified ten distinct clusters of related symptoms.

Pain and SensitizationCognitive Impairment

Pain and SensitizationCognitive Impairment

The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Oosterman, Joukje M, van der Schaaf, Marieke, de Kleijn, Willemien P E et al.·Journal of psychosomatic research·2025

This study looked at how fatigue and pain affect thinking and memory problems in people with ME/CFS. Researchers tested 1,375 patients on tasks like reaction time and attention, and found that both fatigue severity and pain severity were linked to worse cognitive performance. The effects were stronger in older patients, suggesting that age may play a role in how much fatigue and pain impact thinking abilities.

Medication use and symptomology in North American women with myalgic encephalomyelitis/chronic fatigue syndrome.

Pochakom, Angela, MacNevin, Gillian, Madden, Robyn F et al.·Frontiers in medicine·2025

This study surveyed 135 women with ME/CFS in North America to understand what medications they use and how these relate to their symptoms and daily functioning. Most participants were taking an average of 3 medications for ME/CFS-related symptoms, with pain medications being the most common, followed by psychiatric and immune-related medications. Interestingly, the study found a U-shaped pattern: both people using very few medications and those using many medications reported lower physical functioning, while moderate medication use was associated with better functioning.

Interventions

E2 ModerateCohortPEM requiredLongitudinal

Impact of the COVID-19 Pandemic and the 2021 National Institute for Health and Care Excellence Guidelines on Public Perspectives Toward Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Thematic and Sentiment Analysis on Twitter (Rebranded as X).

Khakban, Iliya, Jain, Shagun, Gallab, Joseph et al.·Journal of medical Internet research·2025

Researchers analyzed nearly 900,000 posts about ME/CFS on Twitter from 2010 to 2024 to understand what patients and the public were discussing about the illness. They found that most posts were neutral (47%), but negative posts increased over time, especially after the COVID-19 pandemic and when new UK treatment guidelines were published in 2021. Patients frequently expressed frustration about ME/CFS being dismissed as a mental health condition and celebrated the 2021 guidelines that recognized it as a physical disease.

Sustained illness burden over time among Australians with myalgic encephalomyelitis/chronic fatigue syndrome.

Weigel, Breanna, Eaton-Fitch, Natalie, Thapaliya, Kiran et al.·PloS one·2025

This Australian study followed 32 people with ME/CFS over one year to document how the illness affects their lives. Participants reported an average of 30 symptoms at each check-in, with no improvement over the year, and their quality of life was significantly worse than the general population. The findings show that ME/CFS causes sustained, long-term disability that requires better support and recognition from Australian healthcare and disability services.

E2 ModerateCohortPEM unclearObservational

Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles.

Tobi, Martin, Chaudhari, Diptaraj, Ryan, Elizabeth P et al.·Biomolecules·2025

Researchers compared gut bacteria and immune molecules in the blood of people with long COVID and chronic fatigue syndrome. They found that people with these conditions have unusual patterns of gut bacteria and different levels of immune signaling molecules compared to healthy controls. These differences suggest the immune system and gut health may play a role in why some people develop long-lasting fatigue after infection.

Immune System

Comparative Study Between Cognitive Phenotypes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Multiple Sclerosis.

Aoun Sebaiti, Mehdi, Oubaya, Nadia, Gounden, Yannick et al.·Diagnostics (Basel, Switzerland)·2025

This study compared thinking and memory problems in ME/CFS patients with those in multiple sclerosis (MS) patients, since both conditions can cause similar cognitive issues, fatigue, and pain. Researchers tested 40 people with ME/CFS and 40 with MS using standard memory and attention tests. They found that ME/CFS patients have a specific pattern of cognitive difficulties, particularly problems with consolidating (storing) new information in memory, which is distinct from MS.

Cognitive Impairment

A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long COVID in Scotland: Part I.

Mclaughlin, Marie, Cerexhe, Luke, Macdonald, Eilidh et al.·The American journal of medicine·2025

Researchers surveyed 253 people living with long COVID in Scotland to understand which symptoms are most common and how severe they are. The most frequent symptoms were post-exertional malaise (when activity makes symptoms worse), extreme tiredness, and thinking problems. The study found that people living in areas with more deprivation experienced more symptoms, but factors like vaccination status and age did not significantly affect symptom patterns.

Physical activity and sedentariness levels in patients with post-exertional malaise resulting from post-COVID-19 syndrome.

Elkebir, Kamel-Eddine, Gilbert, Jo-Anne, Kugathasan, Thiffya Arabi et al.·Work (Reading, Mass.)·2025

This study looked at how physical activity changed in 154 people who developed post-exertional malaise (PEM)—extreme tiredness and pain that worsens after activity—following COVID-19. Researchers found that after COVID-19, these patients became much less active and spent more time sitting, especially at work. Women and those with more severe PEM were most affected by these changes.

Exploration of Intersections and Divergences of Long COVID and Chronic Fatigue Syndrome.

Kouyoumdjian, Joao A, Yamamoto, Leticia A, Graca, Carla R·Cureus·2025

This study looked at how Long COVID and ME/CFS might be related by comparing people with Long COVID symptoms to those without and healthy controls. While many Long COVID patients experienced symptoms that overlap with ME/CFS—like post-exertional malaise (feeling worse after activity), brain fog, and sleep problems—only about 1 in 5 Long COVID patients actually met the official diagnostic criteria for ME/CFS. The findings suggest that Long COVID and ME/CFS are related but distinct conditions.

E2 ModerateCohortPEM unclearLongitudinal

Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie et al.·The American journal of medicine·2025

Researchers used advanced brain imaging to measure chemical imbalances in ME/CFS and long COVID patients compared to healthy people. They found that two important brain chemicals—glutamate and N-acetyl-aspartate—were significantly higher in patients with both conditions. These chemical imbalances were connected to how severe patients' symptoms were, suggesting that abnormal brain chemistry may play a role in the exhaustion and other symptoms these patients experience.

Neuroinflammation

Health outcomes up to 3 years and post-exertional malaise in patients after hospitalization for COVID-19: a multicentre prospective cohort study (CO-FLOW).

Berentschot, Julia C, Bek, L Martine, Drost, Manon et al.·The Lancet regional health. Europe·2025

This study followed 299 people hospitalized with COVID-19 for three years after discharge to track their recovery. While some improved over time, many people continued experiencing fatigue, memory problems, and cognitive difficulties—and these problems actually got worse between years 2 and 3. About one-third of patients developed post-exertional malaise (PEM), a condition where activity makes symptoms significantly worse, and these patients had more severe and persistent health problems throughout the study.

E2 ModerateCohortPEM not requiredCross-Sectional

Deep learning analysis of long COVID and vaccine impact in low- and middle-income countries (LMICs): development of a risk calculator in a multicentric study.

Shaheen, Ahmed, Shaheen, Nour, Long COVID Collaboration Study Group in the LMICs et al.·Frontiers in public health·2025

Researchers studied over 2,400 COVID-19 patients in low- and middle-income countries to understand why some people develop long-lasting symptoms like chronic fatigue and depression after infection. They used advanced computer analysis to identify which patients were at highest risk for these prolonged symptoms. The study found that vaccination reduced the risk of developing these long-term problems, and that older age, being female, and smoking were linked to higher risk of chronic fatigue.

E2 ModerateCohortPEM not requiredCross-Sectional

Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA.

Issa, Anindita, Lin, Jin-Mann S, Chen, Yang et al.·Journal of clinical medicine·2025

This study found that people with ME/CFS experience much higher levels of autonomic nervous system problems—which control things like heart rate, blood pressure, and digestion—compared to healthy people. Nearly all ME/CFS patients (97%) had at least one autonomic symptom, with common complaints including dizziness, cold hands and feet, and difficulty standing up. The more autonomic symptoms someone had, especially in certain areas like blood pressure regulation and stomach problems, the more severe their overall illness tended to be.

Autonomic Nervous System

The relationship between fatigue, sleep quality, and sleep deprivation.

Ayas, Fahriye Yonca, Özcebe, Lütfiye Hilal·Sleep & breathing = Schlaf & Atmung·2025

This study looked at how fatigue, sleep quality, and daytime sleepiness are connected in workplace employees. Researchers found that when people have poor sleep quality or don't sleep enough hours, they tend to experience more fatigue and daytime sleepiness—and these problems appear to affect each other in a cycle. The study suggests that addressing sleep problems may be important for reducing fatigue and improving workplace safety.

Sleep

E2 ModerateCohortPEM requiredLongitudinal

Temporal Dynamics of the Plasma Proteomic Landscape Reveals Maladaptation in ME/CFS Following Exertion.

Germain, Arnaud, Glass, Katherine A, Eckert, Melissa A et al.·Molecular & cellular proteomics : MCP·2025

Researchers studied what happens in the blood of ME/CFS patients during and after exercise to understand post-exertional malaise (PEM)—the worsening of symptoms that occurs after physical activity. They measured over 6,000 different proteins in 79 ME/CFS patients and 53 healthy controls before exercise, immediately after, and during recovery. They found that ME/CFS patients have abnormal protein changes during recovery that suggest their immune system and energy-producing cells are not working properly after exertion.

Immune SystemPost-Exertional Malaise

Hippocampal subfield volume alterations and associations with severity measures in long COVID and ME/CFS: A 7T MRI study.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie et al.·PloS one·2025

Researchers used advanced brain imaging to compare a part of the brain called the hippocampus in long COVID patients, ME/CFS patients, and healthy people. They found that certain areas of the hippocampus were larger in both patient groups compared to healthy controls, and these size differences were linked to how severe symptoms like fatigue, pain, and memory problems were. This suggests that changes in brain structure might explain some of the cognitive difficulties these patients experience.

Cognitive Impairment

Understanding symptom clusters, diagnosis and healthcare experiences in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a cross-sectional survey in the UK.

Mansoubi, Maedeh, Richards, Thomas, Ainsworth-Wells, Martine et al.·BMJ open·2025

This large UK survey asked over 8,800 people with ME/CFS or long COVID about their symptoms and experiences with healthcare. The study found that fatigue, brain fog, pain, and sleep problems are the most common symptoms, but people often wait years for a diagnosis. Even after new healthcare guidelines were introduced, most patients said they weren't satisfied with the care they received from the NHS.