Evidence browser

Disequilibrium, Rather than Postural Orthostatic Tachycardia Syndrome, Is the Primary Determinant of Orthostatic Intolerance in Patients with Long COVID.

Miwa, Kunihisa·Journal of clinical medicine·2026

Many long COVID patients experience dizziness and difficulty standing (orthostatic intolerance), but researchers found this is not usually caused by the heart racing when standing up (POTS). Instead, balance problems detected by simple standing tests were the main cause in these patients. When treated with an antibiotic or brain stimulation therapy, most patients with balance-related standing problems improved.

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

E2 ModerateCohortPEM unclearObservational

Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Long COVID.

Barr, Julia, Marsden, Lowri, Dassanayake, Theshan et al.·Journal of clinical medicine·2026

This observational study tested whether a personalised 8-week management plan (involving increased fluid and salt intake, pacing strategies, and calf exercises) was feasible and associated with symptom changes in 22 people with ME/CFS or Long COVID who experienced orthostatic intolerance. Reported improvements were modest: autonomic symptom scores improved by 7.7 points, and heart rate response during a standing test decreased slightly; however, adherence was highly variable, and the authors note that statistical improvements may not reflect clinically meaningful symptom relief. The study remains preliminary and cannot establish whether this protocol is an effective treatment.

InterventionsAutonomic Nervous System

E2 ModeratePEM unclearRegistry-Resource

Risk factors for severe post-COVID condition in children, adolescents, and young adults.

Donath, Quirin, Haegele, Matthias, Schindler, Daniela et al.·European journal of pediatrics·2026

This observational study from a German pediatric hospital followed 120 children and young adults with post-COVID condition (PCC), observing that those with more severe illness were more likely to have had 12 or more symptoms during their initial COVID-19 infection, alongside other acute symptoms such as trouble concentrating and fainting-like episodes. One quarter of participants met criteria for ME/CFS, and all of these were in the severely affected group; by analogy, if similar patterns apply to ME/CFS patients, early identification of high-symptom-burden acute illness might help predict who develops severe long-term illness. These findings are preliminary and come from a single hospital site.

Severe MEAutonomic Nervous SystemDiagnosticsCognitive Impairment

BiomarkersAutonomic Nervous SystemImmune SystemCognitive Impairment

Involvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndrome.

Azcue, N, Prada, A, Del Pino, R et al.·Scientific reports·2026

Researchers compared immune markers called autoantibodies in people with post-COVID condition, ME/CFS, and healthy controls. They found that people with ME/CFS had higher levels of antibodies against certain nerve receptors (β2 adrenergic), and these antibodies were associated with autonomic nervous system problems and memory changes. However, this is a single cross-sectional study, and autoimmunity remains one of several proposed mechanisms—it is not yet clear whether these antibodies are a cause or a consequence of ME/CFS.

BiomarkersInterventionsSleepAutonomic Nervous System

Association between light exposure patterns and multidimensional health outcomes in individuals with myalgic encephalomyelitis/chronic fatigue syndrome: findings from an observational cross-sectional cohort study.

Cambras, Trinitat, Domingo, Joan Carles, Sanmartín-Sentañes, Ramon et al.·Journal of translational medicine·2026

This study observed patterns of light exposure in 100 ME/CFS patients and 56 healthy controls over one week, using wrist-worn devices to track light, activity, and body temperature. Researchers found that ME/CFS patients with more stable daytime light exposure reported lower fatigue, better sleep, and higher quality of life compared to those with irregular or nighttime-dominant light patterns; these associations were not observed in healthy controls. The findings suggest light exposure patterns may be worth studying as a potentially modifiable lifestyle factor, though the study cannot prove that changing light exposure would improve symptoms.

E2 ModerateCohortPEM unclearObservational

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study.

Kim, Laura, Cammà, Guido, Peters, Claudia Kedor et al.·Journal of translational medicine·2026

This observational study of 30 ME/CFS patients reported improvements in physical functioning, fatigue, and pain after 40 sessions of hyperbaric oxygen therapy (HBOT), with associated changes in brain connectivity patterns. However, this is a single-group study without a control arm receiving a sham or alternative treatment, so we cannot yet determine whether observed improvements were due to HBOT itself or other factors such as expectancy or natural variation.

NeuroinflammationInterventionsAutonomic Nervous SystemCognitive Impairment

Understanding concussion in myalgic encephalomyelitis/chronic fatigue syndrome: Findings from the 2023 National Health Interview study.

Sirotiak, Zoe, Adamowicz, Jenna L, Thomas, Emily B K·Brain injury·2026

This study found that people with ME/CFS are nearly 5 times more likely to have had a concussion in the past year compared to people without ME/CFS. People with ME/CFS also experienced more falls and dizziness or balance problems. The researchers suggest that doctors should screen patients with ME/CFS more carefully for concussions and take steps to reduce their concussion risk.

Ocular Symptoms in Long COVID: A Cross-Sectional Study.

Kaleem, Shayaan, Sawano, Mitsuaki, Arun, Adith S et al.·Clinical ophthalmology (Auckland, N.Z.)·2026

This study looked at eye problems in people with long COVID, comparing those who developed new eye symptoms (like blurred vision, dry eyes, or floaters) after infection with those who didn't. About 57% of the 595 participants reported new eye symptoms. People with eye symptoms had worse overall health, more financial struggles, and were more likely to have dysautonomia (problems with blood pressure and heart rate control) and ME/CFS.

E2 ModerateCohortPEM not requiredLongitudinal

Long COVID longitudinal symptoms burden clusters within a national community-based cohort.

Shen, Yanhan, Shahn, Zach, Robertson, McKaylee M et al.·BMC infectious diseases·2026

This study followed over 500 people with long COVID for up to a year, tracking their symptoms over time. Researchers identified three groups based on symptom burden: one with persistent severe symptoms (including fatigue, brain fog, post-exertional malaise, and pain), one with moderate symptoms that improved, and one with minimal symptoms. The findings are preliminary and based on self-reported data, so the stability and generalisability of these groups to other long COVID populations remain to be confirmed.

Pain and SensitizationSleepAutonomic Nervous SystemCognitive Impairment

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.

E2 ModerateCohortPEM requiredCross-Sectional

Exploratory study on autoantibodies to arginine-rich human peptides mimicking Epstein-Barr virus in women with post-COVID and myalgic encephalomyelitis/chronic fatigue syndrome.

Hoheisel, Friederike, Fleischer, Kathrin Maria, Rubarth, Kerstin et al.·Frontiers in immunology·2025

This study looked for certain antibodies in the blood of women with post-COVID and ME/CFS that might mistakenly attack the body's own proteins. The researchers found that patients with these conditions had more of these problematic antibodies than healthy people, and these antibodies were linked to common ME/CFS symptoms like fatigue, brain fog, pain, and autonomic problems. The results suggest that a virus (EBV) may trigger the immune system to attack human proteins that look similar to viral proteins.

Pain and SensitizationAutonomic Nervous SystemCognitive Impairment

Provocation of brachial plexus and systemic symptoms during the elevated arm stress test in individuals with myalgic encephalomyelitis/chronic fatigue syndrome or idiopathic chronic fatigue.

Edwards, Charles C, Byrnes, Julia M, Broussard, Camille A et al.·Journal of translational medicine·2025

Researchers tested whether a simple arm position exercise (holding arms overhead and opening/closing fists) could trigger symptoms in ME/CFS patients who struggle with overhead activities. They found that nearly all patients (97%) developed arm symptoms like pain, numbness, or heaviness during the test, and 41% also experienced whole-body symptoms like dizziness, brain fog, or a racing heart. This suggests that some ME/CFS patients may have nerve compression issues in their shoulders or neck that worsen with certain arm positions.

E2 ModerateCohortPEM unclearObservational

The Relation Between Cardiac Output and Cerebral Blood Flow in ME/CFS Patients with a POTS Response During a Tilt Test.

van Campen, C Linda M C, Visser, Frans C·Journal of clinical medicine·2025

When people with ME/CFS and POTS stand up, their blood pressure and heart rate don't respond normally, causing symptoms like dizziness and fatigue. This study looked at 260 ME/CFS patients during a tilt test to understand how the heart's output of blood relates to blood flow in the brain. The researchers found two different patterns: about two-thirds of patients showed their brain blood flow dropped at roughly the same rate as their heart's output decreased, while about one-third had a different pattern where their heart was racing but their heart output wasn't dropping as much, and their brain blood flow didn't follow the expected pattern.

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.

E2 ModerateCohortPEM requiredObservational

Low Vasopressin in Myalgic Encephalomyelitise/Chronic Fatigue Syndrome.

Huhmar, Helena M, Soinne, Lauri S, Bertilson, Bo Christer et al.·Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·2025

This study found that most people with ME/CFS have abnormally low levels of vasopressin, a hormone that helps your body control water balance and blood volume. The researchers measured this hormone and fluid markers in over 100 ME/CFS patients and discovered that 82% had vasopressin levels below the detectable range. This may help explain why many ME/CFS patients experience excessive thirst, frequent urination, and dizziness when standing up.

E2 ModerateBehavioralPEM not requiredCross-Sectional

Comparing autonomic nervous system function in patients with functional somatic syndromes, stress-related syndromes and healthy controls.

Van Den Houte, Maaike, Ramakers, Indra, Van Oudenhove, Lukas et al.·Journal of psychosomatic research·2025

This study measured how the nervous system responds to stress in people with ME/CFS and similar conditions, compared to healthy people. Researchers found that patients with ME/CFS and stress-related conditions had their 'stress response system' stuck in overdrive even at rest, and this system didn't properly calm down after stress passed. These findings suggest that autonomic nervous system dysfunction—an imbalance in the automatic systems that control heart rate and other vital functions—may be a common feature across these conditions.

Cross-Sectional Study Evaluating the Role of Autonomic Nervous System Functional Diagnostics in Differentiating Post-Infectious Syndromes: Post-COVID Syndrome, Chronic Fatigue Syndrome, and Lyme Disease.

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

This study compared how the nervous system functions differently in people with Post-COVID syndrome, ME/CFS (both COVID-related and unrelated), and late-stage Lyme disease—three conditions that often feel similar but may have different causes. Researchers tested 758 patients using heart rhythm monitors, tilt tests, and blood pressure measurements to see how their bodies responded to position changes and stress. They found that Lyme disease patients showed a distinct pattern of nerve dysfunction (adrenergic failure), while Post-COVID and ME/CFS patients had different types of nervous system imbalances.

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.