Evidence browser

E2 ModerateCohortPEM unclearCase-Control

A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.

Hirsch, Annemarie G, Justice, Anne E, Poissant, Amy et al.·BMC infectious diseases·2025

Researchers studied the genes of people who had Lyme disease to understand why some develop lasting symptoms even after treatment. They found two genetic regions that might be involved in persistent Lyme disease symptoms, with one linked to a protein called MARC2 that affects immune function. When they checked whether these same genetic changes appeared in people with fibromyalgia or ME/CFS, they did not find the same patterns, suggesting these conditions may have different genetic roots.

Immune System

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 not requiredCross-Sectional

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.

Autonomic Nervous System

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.

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 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.

Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia.

Giménez-Orenga, Karen, Pierquin, Justine, Brunel, Joanna et al.·Brain, behavior, & immunity - health·2025

Researchers measured specific proteins and immune markers in the blood of people with post-COVID-19 condition, ME/CFS, and fibromyalgia to see if they could tell these conditions apart. They found that certain blood markers could distinguish post-COVID-19 condition from the other two conditions with very high accuracy, suggesting these illnesses may involve different immune patterns even though their symptoms overlap significantly.

Immune System

Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection.

Hadidchi, Roham, Patel, Bhakti, Madan, Japji et al.·Journal of translational medicine·2025

This study found that people who had COVID-19 are more likely to develop ME/CFS in the years following infection compared to people who never had COVID-19. Women, and people with existing autoimmune or anxiety disorders, appear to be at higher risk. Importantly, having COVID-19 again did not increase the risk further, and blood tests during acute COVID were not able to predict who would later develop ME/CFS.

Long COVID Overlap

E2 ModeratePEM unclearBiobank-Resource

Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms.

Almulla, Abbas F, Maes, Michael, Zhou, Bo et al.·Journal of advanced research·2025

This study found that people with Long COVID have unusual immune responses targeting the brain and nerve cells. Researchers measured antibodies (immune proteins) in people with Long COVID and healthy controls, discovering that Long COVID patients have significantly higher levels of antibodies attacking several brain proteins. These brain-targeted immune responses were strongly linked to fatigue severity and mood symptoms like depression and anxiety.

Neuroinflammation

Defining a High-Quality Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cohort in UK Biobank.

Samms, Gemma L, Ponting, Chris P·NIHR open research·2025

This study looked at how ME/CFS is identified in UK Biobank, a large database of health information from hundreds of thousands of people. Researchers found that about 1 in 100 UK Biobank participants had some evidence of ME/CFS, but only about one-third had strong, consistent evidence across multiple records. When they accounted for people too ill to participate in the study, they estimated that around 410,000 people in the UK have ME/CFS.

Diagnostics

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 not requiredCross-Sectional

Chronicity rhetoric in health and welfare systems inhibits patient recovery: a qualitative, ethnographic study of fibromyalgia care.

Cupit, Caroline, Finlay, Teresa, Pope, Catherine et al.·Social science & medicine (1982)·2025

This study looked at how healthcare and welfare systems talk about fibromyalgia and similar long-term conditions like ME/CFS. Researchers found that when doctors and officials constantly describe these conditions as permanent and unchangeable ('chronicity rhetoric'), it can actually get in the way of patients healing and recovering. The study suggests that changing how we talk about these conditions—and how our support systems are designed—might help patients feel more hopeful and do better.

Diagnostics

An Exploration of How Functional Neurological Disorder Is Discussed on X (Twitter): Mixed Methods Study Using Social Network and Content Analysis.

McLoughlin, Caoimhe, Wang, Jing-Yi, Do, Florence et al.·Journal of medical Internet research·2025

Researchers studied how people talk about Functional Neurological Disorder (FND) on social media platform X (Twitter). They found that most influential voices discussing FND actually dismiss or disagree with the condition, while people with ME/CFS and long COVID have more visibility in these conversations. This matters because online information shapes what patients and the public believe about these conditions.

E2 ModerateCohortPEM not requiredCase-Control

Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study.

Peter, Raphael S, Nieters, Alexandra, Göpel, Siri et al.·PLoS medicine·2025

This study followed nearly 1,000 people who had long-term COVID symptoms for over a year to see who improved and who stayed sick. Researchers found that about two-thirds of patients still had symptoms in the second year after infection, with fatigue, breathing problems, and thinking difficulties being the most common complaints. People who got better tended to have had milder initial infections and were more educated, while those who stayed sick were more likely to be overweight and have had specialist medical care or rehabilitation.

E2 ModerateCohortPEM not requiredCross-Sectional

Efficacy of vitamin D replacement therapy on 28 cases of myalgic encephalomyelitis/chronic fatigue syndrome after COVID-19 vaccination.

Kodama, Shinichiro, Konishi, Nafuko, Hirai, Yuriko et al.·Nutrition (Burbank, Los Angeles County, Calif.)·2025

This study looked at 28 patients who developed ME/CFS after COVID-19 vaccination and found that most had very low vitamin D levels. When these patients received vitamin D treatment through diet, sun exposure, and supplements, their vitamin D levels improved and their ME/CFS symptoms significantly decreased—with 82% of patients no longer meeting ME/CFS criteria after treatment. Sleep problems and autonomic symptoms (like heart rate and blood pressure changes) showed the most improvement.

Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to long COVID.

Al Masoodi, Wasim Talib Mahdi, Radhi, Sami Waheed, Abdalsada, Habiba Khdair et al.·PloS one·2025

This study looked at 90 people, some with Long COVID and some without, to understand why Long COVID patients develop depression, anxiety, and chronic fatigue. Researchers measured several substances in the blood related to inflammation and metabolism. They found that people with Long COVID had higher levels of inflammatory markers and abnormal insulin function, and these changes were linked to their mood and fatigue symptoms.

NeuroinflammationEnergy MetabolismImmune System

E2 ModerateCohortPEM unclearLongitudinal

AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome.

Xiong, Ruoyun, Aiken, Elizabeth, Caldwell, Ryan et al.·Nature medicine·2025

Researchers used artificial intelligence to analyze blood, gut bacteria, immune cells, and symptoms from 249 ME/CFS patients tracked over 4 years. The AI model discovered that ME/CFS involves abnormal patterns in gut bacteria products, blood fats, and immune cells that attack infections—particularly special T cells that become overactive. These findings suggest ME/CFS isn't caused by a single problem but by multiple connected systems going wrong together.

BiomarkersGut MicrobiomeEnergy MetabolismImmune System

E2 ModerateCohortPEM unclearLongitudinal

Cognitive Impairments in Two Samples of Individuals with ME/CFS and Long COVID: A Comparative Analysis.

Sirotiak, Zoe, Adamowicz, Jenna L, Thomas, Emily B K·Journal of clinical psychology in medical settings·2025

This study looked at brain fog and concentration problems in people with ME/CFS and long COVID using data from over 27,000 Americans. Researchers found that people with ME/CFS are about 6 times more likely to experience cognitive difficulties like memory and concentration problems compared to people without these conditions, while long COVID increases the risk about 2 times. People who have both ME/CFS and long COVID together face even greater cognitive challenges.

Long COVID Overlap

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

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.