Evidence browser

E2 ModerateCohortPEM unclearLongitudinal

Association between pre-existing chronic conditions and severity of first SARS-CoV-2 infection symptoms among adults living in Canada: a population-based survey analysis from January 2020 to August 2022.

Cheta, Nicholas, Zakaria, Dianne, Demers, Alain et al.·BMC public health·2025

This Canadian study looked at whether people with long-term health conditions experienced more severe COVID-19 symptoms when they caught the virus. Researchers surveyed over 10,000 adults from 2020 to 2022 and found that certain conditions—like chronic lung disease, high blood pressure, ME/CFS, fibromyalgia, and arthritis—were linked to worse COVID-19 symptoms. This information can help doctors identify who might need extra support or preventive care when facing a COVID-19 infection.

Relationship between post-COVID-19 symptoms and daily physical activity.

Sarmento, Antonio, Webber, Sandra, Sargent, Shelley et al.·Frontiers in rehabilitation sciences·2025

This study tracked 18 people with post-COVID symptoms (11 of whom also had ME/CFS-like symptoms) for a week using smartwatches and daily surveys to see how their symptoms related to how much they walked each day. The researchers found that dizziness had the strongest connection to reduced activity—people with more dizziness walked fewer steps both on the same day and the next day. They also discovered that when people had lower fatigue or chest pain the previous day, they were more likely to walk 5,000 or more steps the next day.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCase-Control

In transfusion-dependent thalassemia, neuronal damage biomarkers are associated with affective and chronic fatigue symptoms.

Ridhaa, Maha Abdul Saheb, Al-Hakeim, Hussein Kadhem, Kahlol, Mohammed K et al.·Scientific reports·2025

This study looked at children with thalassemia, a blood disorder requiring frequent transfusions, to see if brain damage and inflammation might cause depression, anxiety, and chronic fatigue. Researchers measured specific markers of brain injury and inflammation in the blood and found that children with thalassemia had higher levels of these markers and more fatigue and mood symptoms than healthy children. The study suggests that iron buildup from transfusions may damage nerve cells in the brain, leading to these symptoms.

Neuroinflammation

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.

Post-Exertional Malaise

The Relationship Between Hemodynamic Responses During Head-Up Tilt Testing and Parameters of Infection in Post-COVID Syndrome, Chronic Fatigue Syndrome, and Late-Stage Lyme Disease.

Milovanovic, Branislav, Markovic, Nikola, Petrovic, Masa et al.·Viruses·2025

This study examined 1036 patients with post-COVID syndrome, chronic fatigue syndrome, and Lyme disease to understand why they experience dizziness and fainting when standing up. Researchers performed tilt-table tests (where patients lie on a table that tilts upward) and checked for signs of past or ongoing infections through blood tests. They found that patients with evidence of multiple past infections were more likely to have abnormal responses during the tilt test, suggesting that lingering effects from infections may affect the nervous system's ability to control blood pressure and heart rate.

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

Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome.

Collins Hutchinson, Meagan L, Liang, Emily, Fuster, Emily et al.·Autonomic neuroscience : basic & clinical·2025

This study looked at 84 women with connective tissue disorders (HSD/h-EDS) to understand how much autonomic nervous system problems they experience and how these affect their quality of life. The researchers found that these women had severe autonomic symptoms, with nearly 60% also having POTS and about 26% having ME/CFS. Overall, their quality of life was significantly worse than patients with other serious conditions like multiple sclerosis or rheumatoid arthritis.

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.

BiomarkersEnergy Metabolism

Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis.

Rostami-Afshari, Bita, Elremaly, Wesam, McGregor, Neil R et al.·International journal of molecular sciences·2025

Researchers found that people with ME have lower levels of a kidney protein called SMPDL3B in their blood and urine compared to healthy people. This protein is important for keeping the kidney's filtering system working properly. The study also identified several metabolic imbalances in ME patients' blood that are linked to kidney problems. These findings suggest that kidney function may be affected in ME, and this protein could potentially be used as a simple blood test to help understand the disease.

E2 ModerateCohortPEM requiredCross-Sectional

Serum Spike Protein Persistence Post COVID Is Not Associated with ME/CFS.

Fehrer, Annick, Sotzny, Franziska, Kim, Laura et al.·Journal of clinical medicine·2025

Researchers tested whether a piece of the COVID-19 virus (spike protein) lingering in the blood after infection could explain ME/CFS symptoms. They found spike protein in some patients' blood months after COVID, but it was present in similar amounts in people who recovered well and those with ME/CFS. This suggests that leftover spike protein is probably not the main cause of ME/CFS.

Awareness and Perception of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Among Pain Specialists: A Questionnaire-Based Study.

Uygun, Gürsan Güneş, Gözükızıl, Salim Taner, Bilen, Ayşegül·Cureus·2025

This study asked pain doctors in Turkey about their knowledge of ME/CFS and how they evaluate and treat patients with the condition. The results show that many pain specialists aren't familiar with ME/CFS, and some hold misconceptions—like thinking it's a type of depression or that intense exercise will help. This matters because pain doctors could potentially help ME/CFS patients, but they need better education about the condition first.

E2 ModerateCohortPEM unclearRegistry-Resource

Genetic variants associated with chronic fatigue syndrome predict population-level fatigue severity and actigraphic measurements.

Liu, Patrick Z, Raizen, David M, Skarke, Carsten et al.·Sleep·2025

This study looked at whether the genetic factors that cause ME/CFS also influence fatigue levels in people without ME/CFS. Researchers compared movement patterns and body temperature rhythms in people with ME/CFS versus healthy controls, then checked if genetic variations linked to ME/CFS were also connected to fatigue in the general population. They found that people with ME/CFS showed significantly less movement and flatter daily temperature patterns, and some genetic variants associated with ME/CFS were also linked to fatigue symptoms in the broader population.

Unequal access to diagnosis of myalgic encephalomyelitis in England.

Samms, Gemma Louise, Ponting, Chris P·BMC public health·2025

This study examined NHS records from England to understand how many people have ME/CFS and whether diagnosis is fair across different groups. Researchers found that about 100,000 people in England have been officially diagnosed with ME/CFS, but the actual number may be much higher—around 404,000 in the UK. The diagnosis rates varied significantly depending on gender, age, ethnicity, and where people live, suggesting some patients are being missed.

Diagnostics

E2 ModerateCohortPEM not requiredCase-Control

No reduced serum serotonin levels in patients with post-acute sequelae of COVID-19.

Mathé, Philipp, Götz, Veronika, Stete, Katarina et al.·Infection·2025

Researchers compared serotonin levels in the blood of 34 people with long COVID (PASC) and 14 healthy people. Serotonin is a chemical in the body that affects mood and fatigue. The study found no meaningful difference in serotonin levels between the two groups, suggesting that low serotonin is probably not the main cause of long COVID symptoms.

Biomarkers

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.

Distinct white matter alteration patterns in post-infectious and gradual onset chronic fatigue syndrome revealed by diffusion MRI.

Yu, Qiang, Kwiatek, Richard A, Del Fante, Peter et al.·Scientific reports·2025

This study used advanced brain imaging to examine whether two types of ME/CFS—one that starts suddenly after an infection and one that develops gradually—show different patterns of damage in the brain's white matter (the nerve fibers that allow brain regions to communicate). Researchers found that these two types of ME/CFS do indeed show distinct patterns, suggesting they may involve different disease processes. This finding supports the idea that ME/CFS is not a single uniform condition but may require different approaches depending on how it started.