Evidence browser

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.

E2 ModerateMechanismPEM requiredObservational

Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome.

Germain, Arnaud, Giloteaux, Ludovic, Moore, Geoffrey E et al.·JCI insight·2022

Researchers studied 60 ME/CFS patients and 45 healthy people by measuring thousands of chemical substances in their blood before and after intense exercise tests done 24 hours apart. They found that ME/CFS patients had very different chemical patterns in their blood, especially after exercise and during the 24-hour recovery period, suggesting their bodies struggle to respond to and recover from physical exertion in ways that may explain post-exertional malaise (the worsening of symptoms after activity).

Energy MetabolismPost-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment.

Imai, Kazuaki, Yamano, Takafumi, Nishi, Soichiro et al.·Viruses·2022

This study tested a Japanese treatment called epipharyngeal abrasive therapy (EAT) on 58 long COVID patients. The treatment involves applying zinc chloride to the back of the throat to reduce inflammation. Patients received weekly treatments for one month, and three common symptoms—fatigue, headaches, and difficulty concentrating—improved significantly after treatment.

Cognitive Impairment

E2 ModerateCohortPEM requiredProtocol

Multimodal MRI of myalgic encephalomyelitis/chronic fatigue syndrome: A cross-sectional neuroimaging study toward its neuropathophysiology and diagnosis.

Shan, Zack Y, Mohamed, Abdalla Z, Andersen, Thu et al.·Frontiers in neurology·2022

This study used advanced brain imaging to investigate whether ME/CFS is caused by a problem with how the brain's blood vessels respond to neural activity. Researchers scanned the brains of 288 people—including those with ME/CFS, chronic fatigue, fibromyalgia, and healthy controls—while they performed tasks and held their breath, measuring blood flow and brain chemicals. The goal was to find distinctive brain patterns that could objectively diagnose ME/CFS and understand what goes wrong in this disease.

Biomarkers

E2 ModerateCohortPEM unclearCase-Control

Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients.

van Campen, C Linda M C, Visser, Frans C·Medicina (Kaunas, Lithuania)·2022

Some ME/CFS patients experience frequent fainting or near-fainting spells and have been told these are psychological in origin. This study compared brain blood flow in ME/CFS patients with these spells to ME/CFS patients without them during a tilt test (where you're gradually tilted upright). The group with fainting spells showed a much larger drop in blood flow to the brain, suggesting their symptoms have a physical cause rather than a psychiatric one.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredLongitudinal

Incidence of Lyme disease in the United Kingdom and association with fatigue: A population-based, historical cohort study.

Brellier, Florence, Pujades-Rodriguez, Mar, Powell, Emma et al.·PloS one·2022

This study tracked over 2,100 people in the UK who were diagnosed with Lyme disease and compared them to similar people without Lyme disease. Researchers found that people with Lyme disease were much more likely to develop fatigue symptoms afterward, and some developed ME/CFS. Interestingly, the risk was highest when Lyme disease occurred in autumn or winter, though fatigue risks remained elevated even months after the initial infection.

E2 ModerateCohortPEM unclearCase-Control

Revisiting IgG Antibody Reactivity to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Its Potential Application to Disease Diagnosis.

Sepúlveda, Nuno, Malato, João, Sotzny, Franziska et al.·Frontiers in medicine·2022

This study looked at antibody responses to Epstein-Barr virus (EBV), a common virus linked to ME/CFS onset in some patients. Researchers analyzed blood samples from 92 ME/CFS patients and 50 healthy people, testing reactions to over 3,000 EBV proteins. They found that in patients whose ME/CFS started after a suspected EBV infection, two specific viral proteins triggered stronger antibody responses than in healthy controls. These antibody patterns could correctly identify about 83% of infected patients and 72% of healthy people, suggesting they might become useful diagnostic markers.

BiomarkersImmune System

Impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the quality of life of people with ME/CFS and their partners and family members: an online cross-sectional survey.

Vyas, Jui, Muirhead, Nina, Singh, Ravinder et al.·BMJ open·2022

This large international study surveyed 1,418 people with ME/CFS and their family members to understand how the illness affects quality of life for both patients and loved ones. People with ME/CFS reported very low health status (averaging 34 out of 100) with major difficulties in daily activities, pain, and movement, while their family members experienced significant emotional distress including worry, frustration, and sadness, plus practical impacts on family life and finances. The study found that the worse a patient's quality of life is, the worse their family member's quality of life tends to be as well.

E2 ModerateCohortPEM requiredCross-Sectional

Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study.

Cook, Dane B, VanRiper, Stephanie, Dougherty, Ryan J et al.·PloS one·2022

Researchers tested 214 people with ME/CFS and 189 healthy controls using exercise bikes to see how their bodies responded to physical activity. They found that people with ME/CFS had unusual patterns during exercise: they breathed inefficiently, their hearts didn't speed up as much as expected, but they felt the exercise was harder than controls thought it was. These differences remained even when comparing people with similar fitness levels.

Post-Exertional Malaise

Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID.

Tokumasu, Kazuki, Honda, Hiroyuki, Sunada, Naruhiko et al.·Medicina (Kaunas, Lithuania)·2022

This study examined patients with long COVID who developed ME/CFS, a serious condition causing extreme fatigue and worsening after activity. Researchers found that about 17% of long COVID patients met standardized medical criteria for ME/CFS, with fatigue and post-exertional malaise being the most common symptoms. Interestingly, men and women were affected equally in this group, which differs from typical ME/CFS patterns.

Post-Exertional Malaise

Regional gray matter volume correlates to physical and mental fatigue in healthy middle-aged adults.

Putra, Handityo Aulia, Park, Kaechang, Yamashita, Fumio et al.·Neuroimage. Reports·2022

Researchers used brain scans to examine whether the size of certain brain regions relates to how tired people feel, both physically and mentally. In a large group of nearly 1,900 healthy middle-aged adults, they found that specific brain areas showed different sizes depending on fatigue levels—some areas were smaller in people reporting more fatigue, while others were larger. This suggests that brain structure may be connected to how tired we feel, even before someone develops a condition like ME/CFS.

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 SystemPost-Exertional Malaise

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground?

Ryabkova, Varvara A, Gavrilova, Natalia Y, Fedotkina, Tamara V et al.·Diagnostics (Basel, Switzerland)·2022

This Russian study looked at 56 people with ME/CFS and 14 people with post-COVID syndrome to understand how their bodies function differently. The researchers found that both groups had similar patterns of immune system problems, heart rate changes when standing up, and reduced blood flow in small vessels. Importantly, fatigue severity was linked to many other ME/CFS symptoms but not to anxiety or depression.

E2 ModerateCohortPEM requiredCross-Sectional

Alteration of Cortical Volume and Thickness in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Staines, Donald et al.·Frontiers in neuroscience·2022

Researchers used brain imaging to compare the brains of people with ME/CFS to healthy people. They found that people with ME/CFS had some areas of the brain that were thinner and other areas that were larger, particularly in regions involved in thinking and emotion. These brain differences were also connected to how severe symptoms like fatigue, sleep problems, and cognitive difficulties were in each person.

Cognitive Impairment

E2 ModerateBehavioralPEM unclearCross-Sectional

Specifics of chronic fatigue syndrome coping strategies identified in a French flash survey during the COVID-19 containment.

Moncorps, Florence, Jouet, Emmanuelle, Bayen, Sabine et al.·Health & social care in the community·2022

This study looked at how people with ME/CFS cope with their illness during lockdown compared to people with other chronic diseases. Researchers surveyed 93 ME/CFS patients and 99 others with different conditions during France's COVID-19 containment in spring 2020. They found that ME/CFS patients use different coping strategies than those with other recognized illnesses—particularly, they rely less on seeking social support and solving problems directly, but use similar amounts of emotion-focused coping.

Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

O'Neal, Adam J, Glass, Katherine A, Emig, Christopher J et al.·Proteomes·2022

Researchers tested blood samples from ME/CFS patients to look for antibodies against 122 different germs that might trigger the illness. They compared the results to healthy people of similar age, sex, and weight. While they found differences in how men and women with ME/CFS respond to infections, they couldn't identify one specific germ as the culprit.

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis.

Smesam, Hasan Najah, Qazmooz, Hasan Abbas, Khayoon, Sinan Qayes et al.·Journal of personalized medicine·2022

This study looked at 118 people with rheumatoid arthritis (RA, an autoimmune disease affecting joints) and 50 healthy people to understand why RA patients often experience depression, anxiety, and fatigue. Researchers measured immune system markers and psychological symptoms, finding that about 70% of these mental and fatigue symptoms could be explained by the same immune system problems that cause RA itself.