Evidence browser

E2 ModerateCohortPEM not requiredLongitudinal

Chronic Fatigue Exhibits Heterogeneous Autoimmunity Characteristics Which Reflect Etiology.

Danilenko, Olga V, Gavrilova, Natalia Y, Churilov, Leonid P·Pathophysiology : the official journal of the International Society for Pathophysiology·2022

This study found that ME/CFS patients have unusual immune system patterns—specifically, their bodies produce antibodies (immune proteins) that attack their own nervous system tissues. The researchers divided ME/CFS patients into three groups based on cause (viral infection, stress, or unknown origin) and found that different groups had different patterns of these self-attacking antibodies. Importantly, all ME/CFS patients showed elevated levels of antibodies against brain and nerve proteins, which could explain why the illness affects multiple body systems.

Immune System

Altered Effective Connectivity of Resting-State Networks by Tai Chi Chuan in Chronic Fatigue Syndrome Patients: A Multivariate Granger Causality Study.

Li, Yuanyuan, Wu, Kang, Hu, Xiaojie et al.·Frontiers in neurology·2022

This study looked at how a traditional Chinese exercise called Tai Chi Chuan affects the brain in ME/CFS patients. Using brain imaging, researchers found that ME/CFS patients had weaker communication between two important brain networks compared to healthy people. After just one month of Tai Chi Chuan training, this brain communication improved, and patients reported better quality of life, especially with less pain and better physical function.

E2 ModerateCohortPEM unclearObservational

Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection.

Bileviciute-Ljungar, Indre, Norrefalk, Jan-Rickard, Borg, Kristian·Journal of clinical medicine·2022

This study looked at 100 people who had mild COVID-19 but developed long-lasting symptoms afterward. Researchers asked about their pain, fatigue, sleep problems, and quality of life. Three-quarters of the participants reported widespread pain in various parts of their body, and many showed signs of fibromyalgia. The study found that pain is a major problem for people with long COVID and needs better treatment.

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation.

Szewczykowski, Charlotte, Mardin, Christian, Lucio, Marianna et al.·International journal of molecular sciences·2022

Some people with Long COVID have abnormal immune proteins called autoantibodies that attack blood vessel control systems in their bodies. This study found that patients with these specific autoantibodies had reduced blood flow in the tiny vessels at the back of the eye, which may reflect similar problems throughout their whole body and could explain some of their symptoms.

Immune System

E2 ModerateCohortPEM not requiredObservational

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome.

Wang, Zheng, Waldman, Michelle F, Basavanhally, Tara J et al.·Journal of translational medicine·2022

Researchers tested blood samples from 166 ME/CFS patients and 83 healthy people to look for immune system clues that might explain the disease. They found that six specific genes related to immune function were more active in patients with severe, bedridden ME/CFS compared to those with milder disease. The study suggests these genes could potentially be used as biomarkers to identify how severe someone's ME/CFS is and might point toward new treatments.

BiomarkersImmune System

Incidence of post-COVID syndrome and associated symptoms in outpatient care in Bavaria, Germany: a retrospective cohort study using routinely collected claims data.

Donnachie, Ewan, Hapfelmeier, Alexander, Linde, Klaus et al.·BMJ open·2022

This study looked at health insurance records from nearly 400,000 people in Germany who had COVID-19 to see how many developed long COVID symptoms lasting at least 12 weeks. About 14% of COVID-19 patients received a diagnosis of post-COVID syndrome, with the most common symptoms being fatigue, breathing problems, and loss of taste or smell. These symptoms occurred much more often in COVID-19 patients compared to people who had other respiratory infections or no respiratory illness.

Cognitive Impairment

E2 ModerateCohortPEM not requiredObservational

Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults.

Havdal, Lise Beier, Berven, Lise Lund, Selvakumar, Joel et al.·Frontiers in neurology·2022

This study looked at young people (ages 12-25) who had COVID-19 but were not hospitalized, comparing them to people who didn't have COVID-19. Researchers found that COVID-19 patients reported more fatigue and post-exertional malaise (PEM)—a worsening of symptoms after physical activity—and had slightly elevated markers of brain injury in their blood. However, their thinking and memory abilities tested normally, and the blood markers didn't directly correlate with their symptoms.

E2 ModerateCohortPEM unclearLongitudinal

The Significance of Pain Drawing as a Screening Tool for Cervicogenic Headache and Associated Symptoms in Chronic Fatigue.

Bernhoff, Gabriella, Huhmar, Helena M, Rasmussen-Barr, Eva et al.·Journal of pain research·2022

This study looked at whether a simple drawing tool could help identify a specific type of headache (cervicogenic headache) in people with ME/CFS. Researchers found that 42% of ME/CFS patients had a particular pain pattern on their drawings that suggested their headache came from their neck. Patients with this neck-related pain pattern also experienced more dizziness, worse pain, and lower quality of life compared to others.

Pain and Sensitization

Physiological assessment of orthostatic intolerance in chronic fatigue syndrome.

Natelson, Benjamin H, Lin, Jin-Mann S, Blate, Michelle et al.·Journal of translational medicine·2022

This study tested how the bodies of ME/CFS patients respond when they shift from lying down to leaning upright for 10 minutes. Researchers measured heart rate, blood pressure, breathing, and carbon dioxide levels in the blood. They found that 60% of patients showed abnormal responses, with low blood carbon dioxide levels being the most common problem, followed by an excessively fast heartbeat when standing.

Autonomic Nervous System

E2 ModerateCohortPEM requiredCross-Sectional

Chronic Fatigue and Postexertional Malaise in People Living With Long COVID: An Observational Study.

Twomey, Rosie, DeMars, Jessica, Franklin, Kelli et al.·Physical therapy·2022

This study looked at 213 people with long COVID to measure how severe their fatigue and postexertional malaise (PEM—worsening of symptoms after activity) were. Researchers found that over 71% had chronic fatigue as severe as or worse than other serious illnesses, and nearly 59% experienced PEM similar to what people with ME/CFS report. The study highlights that fatigue and symptom flare-ups after activity are major problems that need careful monitoring and should shape how doctors design rehabilitation programs.

E2 ModerateBehavioralPEM not requiredCross-Sectional

The psychological features of distinct somatic syndromes: A cluster analysis according to population-based somatic symptom profiles in Taiwan.

Huang, Wei-Lieh, Chang, Shu-Sen, Liao, Shih-Cheng·Journal of the Formosan Medical Association = Taiwan yi zhi·2022

This study looked at whether different types of physical symptoms (like fatigue, pain, digestive problems, and heart-related symptoms) represent separate conditions or are all part of one bigger syndrome. Researchers analyzed survey data from 550 people in Taiwan and found that people tend to cluster into four different groups based on their symptom patterns, and each group had different levels of depression, anxiety, and health worry.

Cerebral gray matter volume correlates with fatigue and varies between desk workers and non-desk workers.

Putra, Handityo A, Park, Kaechang, Yamashita, Fumio et al.·Frontiers in behavioral neuroscience·2022

This study looked at how fatigue is connected to the size of different brain regions in 1,618 healthy people. Researchers found that people who reported more fatigue had smaller volume in one brain area (supplementary motor area) but larger volume in two other areas (superior parietal lobule and basal forebrain). Interestingly, desk workers and non-desk workers showed different patterns, suggesting that work environment may influence how fatigue affects the brain.

Long-term sequelae of COVID-19 (myalgic encephalomyelitis): An international cross-sectional study.

Shaheen, Nour, Shaheen, Ahmed·Medicine·2022

This study examined how COVID-19 affects people's health long after the initial infection, including whether some people develop ME/CFS (myalgic encephalomyelitis) as a result. Researchers planned to survey 20,000 people worldwide about their ongoing symptoms weeks to months after COVID-19 infection, using detailed questionnaires to capture a wide range of both common and unusual long-term effects. The goal was to understand who develops long-term problems and whether COVID-19 can trigger ME/CFS in previously healthy people.

E2 ModerateBehavioralPEM not requiredLongitudinal

Subjective and objective cognitive function in adolescent with chronic fatigue following Epstein-Barr virus infection.

Øie, Merete Glenne, Rødø, Astrid Sofie Buer, Bølgen, Maria Sletten et al.·Journal of psychosomatic research·2022

This study followed 195 teenagers who had Epstein-Barr virus infection for six months to see if they developed persistent fatigue and cognitive problems. While teenagers with ongoing fatigue reported much more trouble with thinking and memory than healthy teenagers, standard cognitive tests showed no actual differences in their thinking abilities. This suggests that cognitive difficulties in ME/CFS may feel very real to patients but are not always detectable by traditional testing methods.

Cognitive Impairment

E2 ModerateBehavioralPEM not requiredCross-Sectional

Influence of Codiagnosis of Chronic Fatigue Syndrome and Habitual Physical Exercise on the Psychological Status and Quality of Life of Patients with Fibromyalgia.

Hinchado, María Dolores, Otero, Eduardo, Navarro, María Del Carmen et al.·Journal of clinical medicine·2022

This study looked at how fibromyalgia (FM) patients feel psychologically and how their quality of life is affected, especially when they also have ME/CFS. The researchers compared people with FM alone, people with both FM and ME/CFS, and healthy people without either condition. They found that regular physical exercise helped both groups feel less stressed and anxious, but having ME/CFS alongside FM didn't make things worse than FM alone.

E2 ModerateCohortPEM unclearObservational

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

Busatto, Geraldo F, de Araujo, Adriana Ladeira, Castaldelli-Maia, João Mauricio et al.·Psychological medicine·2022

Researchers studied 749 people who had been hospitalized with COVID-19 and assessed them 6-11 months later. They found that 30 different symptoms—including fatigue, brain fog, depression, and anxiety—tend to occur together as part of one underlying condition. People with more severe symptoms also showed signs of ongoing inflammation in their blood and had greater physical disability, suggesting a real biological basis for their illness.

Cognitive Impairment

Activity monitoring and patient-reported outcome measures in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

Rekeland, Ingrid G, Sørland, Kari, Bruland, Ove et al.·PloS one·2022

This study tracked 27 ME/CFS patients for six months using Fitbit activity monitors and questionnaires to understand how symptoms vary day-to-day and whether activity data matches what patients report. Researchers found that people with milder disease had larger swings in their activity levels week-to-week, while those with severe disease stayed consistently low. Activity monitoring proved feasible and useful as a tool alongside patient surveys.

Small-Fiber Polyneuropathy Is Prevalent in Patients With Interstitial Cystitis/Bladder Pain Syndrome.

Wolff, Dylan T, Xu, Raymond, Overholt, Tyler et al.·Urogynecology (Philadelphia, Pa.)·2022

Researchers found that about one-third of people with bladder pain syndrome (IC/BPS) have small-fiber polyneuropathy (SFPN), a condition where tiny nerves in the skin are damaged or reduced. Notably, people with SFPN were significantly more likely to also have chronic fatigue syndrome (31% vs 10.6%). This suggests these two painful conditions may share a common nerve-related mechanism.