Evidence browser

E2 ModerateBehavioralPEM not requiredLongitudinal

The Implications and Predictability of Sleep Reversal for People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Machine Learning Approach.

Dietrich, Meghan P, Pravin, Raam, Furst, Jacob et al.·Healthcare (Basel, Switzerland)·2025

Some people with ME/CFS experience sleep reversal, where they sleep during the day and stay awake at night. This study looked at 2,313 ME/CFS patients to understand how common sleep reversal is and what symptoms go with it. People with sleep reversal reported more severe ME/CFS symptoms overall and greater difficulty with daily activities compared to those with normal sleep patterns.

Sleep

Prospective associations between major depressive disorder, generalized anxiety disorder, fibromyalgia, and myalgic encephalomyelitis/chronic fatigue syndrome.

Thomas, Nathaniel Stembridge, Neale, Michael C, Kendler, Kenneth S et al.·Psychological medicine·2025

This study followed over 100,000 people over time to understand how depression, anxiety, fibromyalgia, and ME/CFS relate to each other. The researchers found that these conditions tend to be connected, but the direction of the connection varies: fibromyalgia appears to lead to depression, while ME/CFS and depression seem to influence each other in both directions. The study suggests that these conditions should be studied separately rather than grouped together, since they may work differently.

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.

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

Clinical heterogeneity in major depressive disorder underlies comorbidity with functional disorders.

Thomas, Nathaniel S, Gillespie, Nathan A, Neale, Michael C et al.·Journal of psychiatric research·2025

This study looked at whether depression and conditions like ME/CFS, fibromyalgia, and IBS occur together more often than chance, and if so, why. Researchers analyzed data from over 10,000 people with depression and found that not all depression symptoms are equally linked to these conditions. They identified five different patterns of depression symptoms, with two patterns being most strongly associated with ME/CFS and related conditions.

Autonomic Dysfunction and Low Cardio-Respiratory Fitness in Long-Term Post-COVID-19 Syndrome.

Cherneva, Radostina, Cherneva, Zheyna, Youroukova, Vania et al.·Biomedicines·2025

This study looked at 192 people who had COVID-19 to understand why some develop long-term fatigue and exercise problems. Researchers measured how well the heart adjusts during exercise and found that people with moderate-to-severe post-COVID symptoms had problems with their autonomic nervous system (the system that controls automatic body functions like heart rate). However, these nervous system problems didn't fully explain why patients had lower exercise capacity.

Autonomic Nervous System

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.

Assessment of Autonomic Nervous System Function in Patients with Chronic Fatigue Syndrome and Post-COVID-19 Syndrome Presenting with Recurrent Syncope.

Milovanovic, Branislav, Markovic, Nikola, Petrovic, Masa et al.·Journal of clinical medicine·2025

This study examined how the autonomic nervous system (the part that controls heart rate, blood pressure, and other automatic functions) works differently in people with ME/CFS compared to healthy people. Researchers tested 440 people, including those with ME/CFS from unknown causes and those whose ME/CFS developed after COVID-19, using heart and blood pressure monitoring tests. They found that both ME/CFS groups had significant problems with autonomic function and experienced fainting or near-fainting episodes at high rates, though the post-COVID group showed somewhat different patterns.

Autonomic Nervous System

A patient-centered view of symptoms, functional impact, and priorities in post-COVID-19 syndrome: cross-sectional results from the Québec Action Post-COVID cohort.

Mayo, Nancy E, Brouillette, Marie-Josée, Falcone, Emilia Liana et al.·BMC infectious diseases·2025

This study surveyed 535 people in Quebec living with long-term COVID symptoms to understand what symptoms they experience, how much these symptoms affect their daily lives, and what treatments matter most to them. The most common symptom was fatigue, and people reported symptoms affecting multiple body systems. Most participants had been dealing with symptoms for over a year, and the impact on their quality of life was significant.

E2 ModerateCohortPEM unclearCase-Control

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

Epstein-Barr virus (EBV) reactivation in post COVID-19.

Shady, Eslam Farid Abu, Ghallab, Abdelhakim Fouad, Shaker, Doaa Abdullah et al.·Auris, nasus, larynx·2025

This study looked at whether a virus called Epstein-Barr virus (EBV) wakes up again in people who have prolonged COVID symptoms like fatigue. Researchers compared 140 people with ongoing COVID fatigue to 80 people who fully recovered from COVID. They found that EBV was reactivated in about 29% of people with persistent fatigue compared to 11% of those who recovered, suggesting EBV reactivation might play a role in long COVID.

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

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

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 unclearObservational

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.

The impact of APOE4 on neurological symptoms after exposure to K. brevis neurotoxin.

Aldrich, Gregory J, Nkiliza, Aurore, Ferguson, Scott et al.·Environmental toxicology and pharmacology·2025

Researchers studied whether a genetic variant called APOE4 makes people more vulnerable to neurological problems from brevetoxins—toxic chemicals released by harmful algae blooms in coastal Florida waters. They found that people carrying the APOE4 gene variant reported more memory problems and fatigue during red tide events compared to those without this variant. This suggests that certain genetic factors may increase how vulnerable someone's brain is to environmental toxins.

Cognitive Impairment

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.