Evidence browser

Assessment of the Gut Microbiome in Patients with Coexisting Irritable Bowel Syndrome and Chronic Fatigue Syndrome.

Chojnacki, Marcin, Błońska, Aleksandra, Kaczka, Aleksandra et al.·Nutrients·2025

This study looked at the gut bacteria and their byproducts in 80 women, comparing those with IBS alone to those with both IBS and chronic fatigue. Women with both conditions had different types of bacteria and different levels of certain chemicals in their urine, particularly those related to tryptophan (an amino acid). Higher levels of some of these chemicals were linked to worse fatigue symptoms.

Gut Microbiome

E2 ModerateCohortPEM not requiredCase-Control

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.

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

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 not requiredObservational

Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity.

Beentjes, Sjoerd Viktor, Miralles Méharon, Artur, Kaczmarczyk, Julia et al.·EMBO molecular medicine·2025

Researchers found multiple blood markers that distinguish ME/CFS patients from healthy people, including signs of inflammation, insulin problems, and liver issues. Importantly, these differences were NOT caused by patients being physically inactive—they are genuine biological changes related to the disease itself. While no single blood test can diagnose ME/CFS yet, these findings suggest that a combination of blood markers could eventually provide objective diagnosis.

E2 ModerateCohortPEM not requiredLongitudinal

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.

Decreased risk of chronic fatigue syndrome following influenza vaccine: a 20-year population-based retrospective study.

Chang, Hsun, Yao, Wei-Cheng, Yu, Teng-Shun et al.·Journal of translational medicine·2025

This study looked at whether getting the flu increases the risk of developing ME/CFS. Researchers tracked nearly 310,000 people who had the flu and compared them to a similar group who did not get the flu over 12 years. They found that people who had the flu were about 50% more likely to develop ME/CFS afterward, but people who received the flu vaccine had lower rates of developing ME/CFS.

E2 ModerateCohortPEM requiredLongitudinal

Incidence and Prevalence of Post-COVID-19 Myalgic Encephalomyelitis: A Report from the Observational RECOVER-Adult Study.

Vernon, Suzanne D, Zheng, Tianyu, Do, Hyungrok et al.·Journal of general internal medicine·2025

This study tracked over 11,000 people who had COVID-19 and about 1,400 who didn't, following them for at least 6 months to see how many developed ME/CFS. Researchers found that people who had COVID-19 were nearly 5 times more likely to develop ME/CFS compared to people who never had COVID-19. About 4.5% of COVID-infected participants developed ME/CFS, compared to only 0.6% of uninfected people.

E2 ModerateCohortPEM unclearLongitudinal

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.

E2 ModerateCohortPEM requiredCross-Sectional

Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction.

Heng, Benjamin, Gunasegaran, Bavani, Krishnamurthy, Shivani et al.·Cell reports. Medicine·2025

This study examined blood samples from ME/CFS patients and healthy people to understand what goes wrong in the body. Researchers found that immune cells in ME/CFS patients are struggling to make energy (ATP), the fuel that powers our cells. The immune system also showed signs of being immature or worn out, and blood proteins related to clotting and blood vessel problems were elevated, suggesting blood vessel dysfunction may contribute to ME/CFS symptoms.

BiomarkersImmune System

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.

Multiple voxel pattern analysis shows associations between chronic fatigue syndrome and cortical atrophy.

Wu, Kang, Zou, Yihuai, Li, Yuanyuan et al.·Frontiers in neuroscience·2025

Researchers used specialized brain imaging to compare 37 people with ME/CFS to 34 healthy people and found that certain areas of the brain's outer layer are thinner in patients with ME/CFS. These thinner areas were linked to how severe their fatigue, pain, and reduced quality of life were. The study suggests that ME/CFS may involve physical changes in brain structure that could help explain why patients experience such debilitating fatigue.

Immune SystemLong COVID Overlap

Comparable Immune Alterations and Inflammatory Signatures in ME/CFS and Long COVID.

Petrov, Steliyan, Bozhkova, Martina, Ivanovska, Mariya et al.·Biomedicines·2025

This study compared immune system markers in people with ME/CFS and Long COVID to those of healthy individuals. Both patient groups showed similar immune problems: lower levels of protective immune cells and higher levels of inflammatory substances in their blood. The findings suggest that ME/CFS and Long COVID may involve very similar underlying immune dysfunction.

E2 ModerateCohortPEM unclearCase-Control

Killer cell immunoglobulin-like receptor (KIR) alleles suggested to be associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Ramadan, Donia Jamal, Kichula, Katherine M, Tao, Sudan et al.·Brain, behavior, and immunity·2025

This study examined specific genetic variations in natural killer (NK) cells—immune cells that help fight infections—in people with ME/CFS compared to healthy people. Researchers found that certain genetic variants were more common in ME/CFS patients while others were less common, suggesting that differences in how NK cells are regulated may play a role in ME/CFS. This supports the idea that immune system dysfunction is involved in the condition.

Immune System

E2 ModerateCohortPEM unclearCase-Control

SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis.

Rostami-Afshari, Bita, Elremaly, Wesam, Franco, Anita et al.·Journal of translational medicine·2025

Researchers identified a protein called SMPDL3B that appears to be elevated in people with ME/CFS and linked to symptom severity. This protein is found in the blood at higher levels in ME patients, particularly in women, and seems to be influenced by hormones and immune system dysfunction. The study also tested two existing diabetes medications (vildagliptin and saxagliptin) in the laboratory and found they could potentially help restore balance to this protein, suggesting a possible new treatment approach.

BiomarkersImmune System

E2 ModerateCohortPEM unclearLongitudinal

Gastrointestinal Barrier Disruption in Post-COVID Syndrome Fatigue Patients.

Rohrhofer, Johanna, Wolflehner, Viktoria, Schweighardt, Johannes et al.·Allergy·2025

This study looked at whether problems with the digestive system might help explain why some people develop long-lasting fatigue and other symptoms after COVID-19 (post-COVID syndrome). The researchers found that people with post-COVID fatigue had signs of gut inflammation and a leaky intestinal barrier, along with changes in immune markers in their blood. This suggests that COVID-19 may damage the gut in ways that contribute to long-term fatigue and post-exertional malaise.

Immune SystemPost-Exertional Malaise

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.

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.