Evidence browser

Wearable technology in the management of complex chronic illness: preliminary survey results on self-reported outcomes.

Sawyer, Abbey, Preston, Rory, Leeming, Harry et al.·Frontiers in digital health·2025

This study looked at whether a smartphone app with a wearable armband helps people with ME/CFS and Long COVID manage their energy and symptoms. Over 1,300 people with these conditions used the app and answered questions about whether it helped them. Most people who used the app for at least a month reported feeling like they better understood their energy limits and how to manage daily activities, though some improvements may have simply come from tracking their own experience over time.

Putting the PASC Score to the Test: Clinical vs. Statistical Accuracy in Long COVID Diagnosis.

Azola, Alba, Dastgheyb, Raha M, Easter, Rebecca et al.·Journal of general internal medicine·2025

Researchers tested a scoring tool called the PASC score to see if it could correctly identify long COVID patients. They compared 130 long COVID patients with 60 people who recovered completely from COVID-19. The PASC score was very accurate at confirming who had long COVID, but missed about 20% of actual patients. A simpler approach using just three symptoms (loss of smell/taste, post-exertional malaise, or sexual dysfunction) worked even better at catching long COVID cases.

Examining Well-Being and Cognitive Function in People With Long COVID and ME/CFS, and Age-Matched Healthy Controls: A Case-Case-Control Study.

Sanal-Hayes, Nilihan E M, Mclaughlin, Marie, Hayes, Lawrence D et al.·The American journal of medicine·2025

This study compared how people with long COVID and ME/CFS experience their daily well-being and thinking abilities, compared to healthy people of similar ages. Researchers found that both long COVID and ME/CFS patients reported similar struggles with fatigue, pain, sleep problems, anxiety, and difficulty with everyday activities—but their actual test performance on thinking tasks was comparable to healthy controls. The findings suggest that both conditions affect quality of life in very similar ways.

E2 ModerateCohortPEM requiredObservational

Low-dose rapamycin alleviates clinical symptoms of fatigue and PEM in ME/CFS patients via improvement of autophagy: a pilot study.

Ruan, Brian T, Bulbule, Sarojini, Gile, Brooke et al.·Journal of translational medicine·2025

Researchers tested a low-dose drug called rapamycin in 86 ME/CFS patients to see if it could reduce fatigue and post-exertional malaise (PEM). About 74% of patients who completed the first month showed improvements in fatigue, PEM, and other symptoms, and the drug appeared safe with no serious side effects. The study suggests that rapamycin may work by fixing a cellular process called autophagy, which appears to be broken in ME/CFS patients.

Immune SystemPost-Exertional Malaise

Clinical and Laboratory Characteristics of Fatigue-Dominant Long-COVID Subjects: A Cross-Sectional Study.

Lee, Jin-Seok, Choi, Yujin, Joung, Jin-Yong et al.·The American journal of medicine·2025

This study looked at 100 people with long COVID who experience significant ongoing fatigue, similar to ME/CFS. Researchers measured fatigue levels and checked blood levels of cortisol (a stress hormone) and other immune markers. They found that people with lower cortisol levels reported worse fatigue and lower quality of life, suggesting a possible connection between this hormone and fatigue severity.

Deoxygenation Trends and Their Multivariate Association with Self-Reported Fatigue in Post-COVID Syndrome.

Ladek, Anja-Maria, Lucio, Marianna, Weiß, Andreas et al.·Biomedicines·2025

This study looked at oxygen levels in the muscles of 100 people with long COVID and 50 healthy controls while they performed light exercise (squeezing a stress ball). The researchers used a special non-invasive scan called NIRS to measure this. People with long COVID, especially those with post-exertional malaise, showed abnormal oxygen patterns in their muscles compared to healthy people, and this was linked to their fatigue levels.

E2 ModerateDiagnosticPEM unclearMethods-Paper

Reliability and validity of the German version of the DePaul Symptom Questionnaire Post-Exertional Malaise (DSQ-PEM).

Kuczyk, Charlotte, Nöhre, Mariel, Herrmann-Lingen, Christoph et al.·Frontiers in psychiatry·2025

Researchers tested a German-language questionnaire designed to measure post-exertional malaise (PEM)—the worsening of symptoms that happens after physical or mental activity in ME/CFS and long COVID. They found the questionnaire is reliable and accurately distinguishes between people with and without long COVID, making it a useful tool for German-speaking patients and doctors.

E2 ModerateCohortPEM requiredCase-Control

Haptoglobin phenotypes and structural variants associate with post-exertional malaise and cognitive dysfunction in myalgic encephalomyelitis.

Moezzi, Atefeh, Ushenkina, Anastasiya, Widgren, Anna et al.·Journal of translational medicine·2025

Researchers studied a protein called haptoglobin in people with ME/CFS and found it may be connected to post-exertional malaise (that worsening of symptoms after activity) and brain fog. They discovered that certain genetic variations of this protein were more common in ME/CFS patients, and those variations were linked to worse symptoms and cognitive problems. The study suggests haptoglobin could be a useful marker to help doctors understand why ME/CFS symptoms vary between patients.

BiomarkersPost-Exertional Malaise

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.

E2 ModerateCohortPEM requiredObservational

The Clinical Relevance of Mast Cell Activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Rohrhofer, Johanna, Ebner, Lilian, Schweighardt, Johannes et al.·Diagnostics (Basel, Switzerland)·2025

This study looked at whether mast cells—immune cells that release chemicals causing inflammation—play a role in ME/CFS. Researchers surveyed 687 ME/CFS patients and reviewed records from 383 others, finding that about 25% had signs of problematic mast cell activation. Importantly, patients with mast cell problems who received targeted treatment reported better symptom relief than those without mast cell involvement, suggesting this might be a treatable subtype of ME/CFS.

Immune SystemPost-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

Patient-reported treatment outcomes in ME/CFS and long COVID.

Eckey, Martha, Li, Peng, Morrison, Braxton et al.·Proceedings of the National Academy of Sciences of the United States of America·2025

This study asked nearly 4,000 ME/CFS and long COVID patients about their experiences with over 150 different treatments to see which ones helped them feel better. The researchers found that ME/CFS and long COVID are very similar illnesses with overlapping symptoms and that patients with each condition responded similarly to treatments. The study also discovered that different patient subgroups—like those with heart rate and blood pressure problems, or those with thinking and memory problems—benefited most from specific types of treatments.

Brain and muscle chemistry in myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and long COVID: a 7T magnetic resonance spectroscopy study.

Godlewska, Beata R, Sylvester, Amy L, Emir, Uzay E et al.·Molecular psychiatry·2025

Researchers used advanced brain scans to look at chemical differences in the brains and muscles of people with ME/CFS, long COVID, and healthy people. They found that people with ME/CFS had higher levels of lactate (a chemical related to energy use) in specific brain areas, suggesting their brains may be working harder to produce energy. People with long COVID showed different changes - lower levels of a chemical called choline in the brain. These findings suggest that ME/CFS and long COVID may have different underlying causes, even though they produce similar symptoms.

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.

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.

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.

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.

A Signal for Voice and Speech Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Grach, Stephanie L, Seltzer, Jaime, Orbelo, Diana M·Journal of clinical medicine·2025

This study explored whether people with ME/CFS experience changes in their voice or speech. Researchers surveyed 685 people with ME/CFS and reviewed open-ended responses from 302 participants. About 9% of respondents mentioned voice or speech changes when describing their disease experience, suggesting this is a real symptom that deserves further attention.

Fatigue, interoplastic and nociplastic distress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Illness, and chronic idiopathic fatigue.

Chen, Emily, Rudder, Tamera, Nwankwere, Charles et al.·Frontiers in neuroscience·2025

This study compared pain sensitivity and fatigue in people with ME/CFS, Gulf War Illness, and chronic fatigue to understand what causes their symptoms. Researchers found that people with ME/CFS and Gulf War Illness have increased pain sensitivity (measured by pressing on their skin), and their pain and internal body sensations are closely linked. However, pain sensitivity didn't strongly correlate with fatigue levels, suggesting that fatigue may involve different mechanisms than pain.