Evidence browser

BiomarkersSleepLong COVID Overlap

Facility-Measured Sleep Electroencephalographic Microstructures in Long COVID.

Sun, Haoqi, Dang, Rammy, Li, Peng et al.·Sleep·2026

Researchers used overnight brain-wave recordings (EEG) to examine sleep patterns in people with long COVID and ME/CFS, comparing them to healthy controls. They found that both groups showed altered patterns in specific brain-wave features during sleep—such as changes in slow waves and sleep spindles (brief bursts of brain activity)—that may be associated with the unrefreshing sleep and fatigue these patients report. However, this is one study in a specific research setting, and it remains unclear whether these brain-wave changes are a cause of the symptoms or simply occur alongside them.

BiomarkersGut MicrobiomeEnergy MetabolismLong COVID Overlap

Comparative Gut Microbiome Alterations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID-19 Syndrome.

Donchev, Deyan, Nikolova, Ralitsa, Vaseva, Katya et al.·Biomedicines·2026

Researchers compared gut bacteria in people with ME/CFS, long COVID, and healthy controls using stool samples. They observed that both ME/CFS and long COVID showed similar patterns of bacterial changes—including more of a bacterium called Sutterella and less of others—compared to healthy people, though the two conditions were not identical. The strongest links between bacterial patterns and symptoms were observed in fatigue and physical symptoms, though this is one study and findings require confirmation in larger follow-up research.

BiomarkersCognitive ImpairmentLong COVID Overlap

Microstructural alterations in brain tissue of ME/CFS and long COVID using diffusion tensor imaging and diffusion kurtosis imaging.

Singh, Tanoj Bahadur, Marshall-Gradisnik, Sonya, Barnden, Leighton et al.·Frontiers in medicine·2026

Researchers used specialized brain imaging scans (DTI and DKI) to observe differences in brain tissue structure between people with ME/CFS, people with long COVID, and healthy controls. They found that ME/CFS and long COVID showed microstructural changes in different brain regions, though the study is cross-sectional and cannot explain why these changes occur or what role they play in symptoms. These are preliminary findings that require replication in larger groups.

E2 ModerateCohortPEM unclearLongitudinal

Two-timepoint multidomain follow-up of post-COVID condition and ME/CFS: overlapping autonomic, small-fiber, and cognitive changes.

Azcue, N, Barranco, C, Tijero-Merino, B et al.·Journal of translational medicine·2026

Researchers compared 21 people with post-COVID condition and 17 people with ME/CFS over about 2.5 years, measuring nerve function, autonomic symptoms, and cognitive performance. They observed that both groups showed similar patterns of changes over time—including worsening processing speed and cold sensation sensitivity, but improving heat sensation thresholds and verbal memory. While the two conditions appeared increasingly alike on follow-up testing, the study does not establish whether they are truly the same disease or simply share overlapping symptoms.

Pain and SensitizationAutonomic Nervous SystemDiagnosticsCognitive Impairment

BiomarkersDiagnosticsImmune SystemLong COVID Overlap

Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID.

Petrov, Steliyan, Bozhkova, Martina, Ivanovska, Mariya et al.·International journal of molecular sciences·2026

Researchers compared immune cell patterns in 103 people with ME/CFS, 63 with long COVID, and 41 healthy controls using blood tests. They observed that ME/CFS and long COVID show different patterns of immune cell activity—long COVID appeared to show persistent immune activation, while ME/CFS appeared associated with reduced immune signalling. These are early findings from one study and do not yet tell us what causes either condition or how to treat it.

Severe MEDiagnosticsLong COVID OverlapPost-Exertional Malaise

Cardiopulmonary Exercise Testing Reveals Functional Limitations and Work Disability in Severe Post-COVID-19 and ME/CFS Patients.

Tomaskovic, Aleksandar, Weber, Vincent, Ochmann, David T et al.·Sports medicine - open·2026

A cross-sectional study of 92 severely ill post-COVID patients found that those meeting ME/CFS criteria had lower measured aerobic capacity (oxygen uptake and power output) on exercise testing compared to post-COVID patients without ME/CFS. Two-thirds of all patients showed objective signs of work disability on testing, and these measurements correlated with patients' own reports of disability and their employment status. The relevance of these findings specifically to ME/CFS requires caution, as the study enrolled primarily post-COVID patients, and the overlap between these conditions remains incompletely understood.

BiomarkersEnergy MetabolismImmune SystemLong COVID Overlap

Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Ikeda, Gentaro, Koike-Ieki, Mariko, Inoue, Hiroyuki et al.·Open forum infectious diseases·2026

Researchers analyzed tiny cell particles called extracellular vesicles in blood samples from people with Long COVID, ME/CFS, and healthy controls. They observed that both Long COVID and ME/CFS groups had elevated levels of certain immune cell-derived particles and alterations in mitochondrial (energy-producing) markers within B cells and other immune cells, though the findings were not identical between groups. These preliminary results suggest there may be shared immune and metabolic changes in these conditions, but the meaning of these changes for patient health remains unclear and needs further study.

E2 ModerateCohortPEM not requiredObservational

Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases.

Ghali, Alaa, Lavigne, Christian, Ghali, Maria et al.·Journal of clinical medicine·2026

A French hospital study observed that post-COVID patients infected in 2020–2021 reported post-exertional malaise (PEM) more often than those infected later, and that PEM was associated with higher fatigue levels. By analogy, this may be relevant to ME/CFS patients, though the study examined post-COVID populations and the reasons for these differences remain uncertain—they could reflect changes in the virus, vaccination, immunity, or other unmeasured factors.

Long COVID OverlapPost-Exertional Malaise

BiomarkersEnergy MetabolismCognitive ImpairmentLong COVID Overlap

Haptoglobin Phenotypes Stratify Post-Exertional Cognitive Dysfunction Associated with Altered Cerebral Oxygenation and Metabolic Signatures in Long COVID.

Moezzi, Atefeh, Elremaly, Wesam, Leveau, Corinne et al.·International journal of molecular sciences·2026

This study observed that Long COVID patients with different versions of a protein called haptoglobin showed different patterns of cognitive problems after physical exertion. Patients carrying certain haptoglobin variants (Hp2) reported worse fatigue and cognitive decline following a challenge test, while those with the Hp1-1 variant showed better cognitive resilience. The findings are preliminary and come from a small group; larger studies are needed to confirm whether haptoglobin type could help identify which Long COVID patients are at higher risk for these cognitive changes.

E2 ModerateCohortPEM unclearCase-Control

Circulating extracellular vesicles-microRNAs as potential biomarkers for the identification of ME/CFS: differentiating fatigue-related conditions.

Eguchi, Akiko, Kuratsune, Hirohiko, Nakatomi, Yasuhito et al.·Journal of translational medicine·2026

Researchers analysed tiny particles called extracellular vesicles in blood samples from patients with ME/CFS, chronic fatigue without a known cause, and depression, looking for differences in small RNA molecules that could help diagnose ME/CFS. They found a pattern of 114 different RNA molecules that appeared associated with ME/CFS and were rarely seen in healthy people, though these findings come from a small group of patients and have not yet been replicated in larger studies.

NeuroinflammationBiomarkersDiagnosticsLong COVID Overlap

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.

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.

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 not requiredCross-Sectional

Unmasking the Long-Term Effects of COVID-19 With a Focus on Chronic Fatigue Syndrome: A Community-Based Study From India.

Gupta, Arti, Rajan, Vishnu, Aravindakshan, Rajeev et al.·Cureus·2025

This study looked at 500 COVID-19 survivors in rural India to see how many developed chronic fatigue syndrome (CFS)—a condition causing severe, lasting tiredness and other symptoms. About 21% of the COVID-19 survivors developed CFS, with older people, women, and those with existing health conditions at higher risk. The study found that fatigue, joint pain, and muscle pain were common problems after COVID-19.

E2 ModerateCohortPEM requiredLongitudinal

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection.

Unger, Elizabeth R, Lin, Jin-Mann S, Wisk, Lauren E et al.·JAMA network open·2024

This study followed over 4,300 people for up to 12 months to see whether COVID-19 infection caused ME/CFS-like symptoms. Researchers found that about 3-4% of people reported ME/CFS-like symptoms after their acute illness, but this rate was similar whether they had tested positive or negative for COVID-19. The results suggest that while some people do develop long-lasting symptoms after illness, COVID-19 may not be uniquely causing ME/CFS more often than other infections.

DiagnosticsLong COVID Overlap

Sleep and circadian rhythm alterations in myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID fatigue syndrome and its association with cardiovascular risk factors: A prospective cohort study.

Zerón-Rugerio, María Fernanda, Zaragozá, Maria Cleofé, Domingo, Joan Carles et al.·Chronobiology international·2024

This study looked at sleep patterns and daily body rhythms in ME/CFS patients and compared them to healthy people. Researchers found that ME/CFS patients had lower activity levels, worse sleep quality, and unhealthy cholesterol levels compared to healthy controls. The study also found that problems with blood vessel function may connect sleep disruptions to heart health problems in ME/CFS patients.

E2 ModeratePEM unclearRegistry-Resource

Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study.

Reuken, P A, Besteher, B, Finke, K et al.·European archives of psychiatry and clinical neuroscience·2024

This study followed over 1,000 people who had long-lasting symptoms after COVID-19 infection. Researchers found that about 31% of patients met the diagnostic criteria for ME/CFS at their first visit, but this dropped to 19% at a second visit months later. While patients reported feeling less fatigued and having fewer concentration problems over time, many continued to experience long-lasting symptoms that significantly affected their daily lives.

Cognitive ImpairmentLong COVID Overlap

E2 ModerateCohortPEM not requiredObservational

Risk of chronic fatigue syndrome after COVID-19: A retrospective cohort study of 3227281 patients.

Chen, Chih-Wei, Lee, Hsun-Hua, Chang, Shu-Hao et al.·Journal of infection and public health·2024

This study looked at over 6 million patient records to compare people who had COVID-19 with people who didn't. Researchers found that people who had COVID-19 were about 1.6 times more likely to develop chronic fatigue syndrome (CFS) afterward. The increased risk appeared in people of all ages, both sexes, and different racial backgrounds.