Evidence browser

Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness.

Boruch, Alexander E, Lindheimer, Jacob B, Ninneman, Jacob V et al.·Brain, behavior, & immunity - health·2023

This study looked at whether post-exertional malaise (PEM)—the worsening of symptoms after physical activity—is caused by changes in gene activity in Gulf War illness patients. Veterans with Gulf War illness and healthy controls exercised on stationary bikes, and researchers measured gene expression in blood samples before and after exercise. While the study found that certain genes did change after exercise in Gulf War illness patients, these gene changes did not explain why their symptoms got worse.

Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.

Achleitner, Martin, Steenblock, Charlotte, Dänhardt, Juliane et al.·Molecular psychiatry·2023

Researchers tested a treatment called therapeutic apheresis (a blood-cleaning procedure) in Long-COVID patients and found that those who improved had significant reductions in harmful immune molecules, fatty substances, and inflammatory markers in their blood. The study also showed that a blood protein called fibrinogen dropped by 70% after treatment, and abnormal blood clumping patterns disappeared. This suggests the treatment may work by removing specific harmful substances from the blood.

E3 PreliminaryCohortPEM requiredObservational

Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents.

Körner, Robert Walter, Bansemir, Ole Yannick, Franke, Rosa et al.·Children (Basel, Switzerland)·2023

This study examined 28 children and teens who developed long-lasting symptoms after COVID-19 infection. The researchers found that most patients had allergies and unusually high levels of immune proteins called IgE, IgG3, and IgG4. About three in ten patients also met criteria for ME/CFS, experiencing severe fatigue, breathing problems, and post-exertional malaise (feeling worse after activity). Most patients gradually improved over about a year, though some took longer to recover.

E3 PreliminaryMechanismPEM requiredMechanistic

Stress-Induced Transcriptomic Changes in Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Reveal Disrupted Immune Signatures.

Van Booven, Derek J, Gamer, Jackson, Joseph, Andrew et al.·International journal of molecular sciences·2023

This study looked at how the bodies of women with ME/CFS respond to exercise compared to healthy women. Researchers collected blood samples at three points: before exercise, during maximum effort, and during recovery. While healthy women's immune cells showed normal changes during exercise, women with ME/CFS showed unusual immune system activity specifically during the recovery period—the time when post-exertional malaise (worsening of symptoms) typically occurs.

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Development and measurement properties of the PEM/PESE activity questionnaire (PAQ).

Davenport, Todd E, Stevens, Staci R, Stevens, Jared et al.·Work (Reading, Mass.)·2023

This study created and tested a new questionnaire called the PAQ that helps measure how post-exertional malaise (PEM) affects a person's ability to do everyday activities. Patients chose three activities that were important to them and rated how much their performance had changed compared to their good days and before they got sick. The questionnaire was given to 675 people twice to make sure it reliably measured the same thing each time, and the results showed it works well.

Sex-Dependent Transcriptional Changes in Response to Stress in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Project.

Gamer, Jackson, Van Booven, Derek J, Zarnowski, Oskar et al.·International journal of molecular sciences·2023

This study looked at how genes behave differently in men and women with ME/CFS when their bodies are stressed by exercise. Researchers tested blood samples from 33 ME/CFS patients and 34 healthy people before, during, and after exercise. They found that men and women with ME/CFS showed different patterns of gene activity in response to exercise—men's immune systems showed more dramatic changes, while women's genes related to stress response and virus handling showed bigger changes.

E3 PreliminaryGuidelinePEM requiredGuideline

Cardiovascular Considerations in the Management of People With Suspected Long COVID.

Quinn, Kieran L, Lam, Grace Y, Walsh, Jillian F et al.·The Canadian journal of cardiology·2023

This review examines how doctors should evaluate and treat heart-related symptoms in people with long COVID. It highlights that about 15% of Canadians infected with COVID-19 develop persistent symptoms lasting more than 12 weeks, including fatigue, shortness of breath, chest pain, and irregular heartbeats. The authors emphasize that doctors need to consider conditions like ME/CFS, postexertional malaise (symptom flare-ups after activity), and dysautonomia (problems with the autonomic nervous system) when evaluating these patients.

Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID.

Edward, Justin A, Peruri, Adithya, Rudofker, Eric et al.·Journal of cardiopulmonary rehabilitation and prevention·2023

Long COVID causes severe fatigue and difficulty exercising, affecting 25-30% of people who had COVID-19. This review suggests that carefully designed exercise programs—tailored to avoid making symptoms worse—may help Long COVID patients recover better. The authors argue that much of Long COVID comes from the body becoming deconditioned (out of shape) from inactivity, and that gentle, personalized exercise can help reduce symptoms.

E3 PreliminaryBehavioralPEM requiredCase-Control

A patient who recovered from post-COVID myalgic encephalomyelitis/chronic fatigue syndrome: a case report.

Oka, Takakazu·BioPsychoSocial medicine·2023

This case report describes a nurse who developed ME/CFS symptoms after recovering from COVID-19, including severe fatigue, pain, brain fog, and heart palpitations that lasted over 6 months. She received treatment combining dietary advice, supplements, behavioral strategies, exercise conditioning, and two medications (amitriptyline and a Japanese herbal medicine called hochuekkito), and eventually recovered fully and returned to work. This is the first detailed report showing that someone with post-COVID ME/CFS can recover with comprehensive multimodal treatment.

E3 PreliminaryMechanismPEM requiredMechanistic

Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles.

Aschman, Tom, Wyler, Emanuel, Baum, Oliver et al.·Acta neuropathologica communications·2023

Researchers examined muscle tissue from people with long COVID who experience fatigue and worsening symptoms after activity. They found that these patients had fewer blood vessels in their muscles, thicker vessel walls, and signs of immune cells that might have been triggered by the initial infection. These physical changes in the muscle's blood supply could explain why exercise makes their symptoms worse.

NeuroinflammationPost-Exertional Malaise

Chronic inflammation, neuroglial dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome.

Chaves-Filho, Adriano Maia, Braniff, Olivia, Angelova, Angelina et al.·Brain research bulletin·2023

This study examines how long COVID and ME/CFS may share similar problems in the body, particularly chronic inflammation (ongoing swelling and immune activation) and low levels of plasmalogens, which are protective fats found in cell membranes. The researchers propose that restoring plasmalogen levels through dietary supplements could potentially help reduce symptoms like fatigue, brain fog, and post-exertional malaise in both conditions.

The Long Road of Long COVID: Specific Considerations for the Allergist/Immunologist.

Bellanti, Joseph A, Novak, Peter, Faitelson, Yoram et al.·The journal of allergy and clinical immunology. In practice·2023

Long COVID is a condition that develops after a COVID-19 infection and can cause symptoms affecting many parts of the body, including heart problems, blood clots, fatigue, and autoimmune issues. This review examines what causes Long COVID and which patients are most at risk, noting that certain groups like Hispanic and Latino communities face higher rates. The authors highlight that while vaccines help prevent severe acute COVID, we still need more research to understand how they affect Long COVID development and progression.

E3 PreliminaryGuidelinePEM unclearGuideline

[Post-COVID Rehabilitation].

Küst, Jutta, Disko, Andreas, Calendo, Luigi Riccardo et al.·Praxis·2023

This guideline explains how to help people recover from post-COVID illness, which can cause lasting fatigue and memory problems that make it hard to work or manage daily life. Since there is no cure yet, treatment focuses on rehabilitation that is tailored to each patient's symptoms and goals, with special attention to gradually rebuilding activity while watching for post-exertional malaise—a worsening of symptoms after physical or mental effort. The approach involves multiple healthcare professionals working together to adjust the workload based on how the patient is doing over time.

NeuroinflammationImmune SystemPost-Exertional Malaise

Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID.

Tate, Warren P, Walker, Max O M, Peppercorn, Katie et al.·International journal of molecular sciences·2023

ME/CFS is a complex illness that typically starts after a viral infection, though other stressful events can also trigger it. This review explains that different patients experience different combinations of symptoms and respond differently to treatments—what helps one person may not help another. The authors discuss how the immune system may shift from a temporary response to a lasting problem, and how the brain's immune system may cause the neurological symptoms people experience.

Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases.

Gottschalk, Carl Gunnar, Peterson, Daniel, Armstrong, Jan et al.·Infectious agents and cancer·2023

This review article examines how viral infections—including long COVID, EBV, and others—can trigger severe, lasting fatigue and related symptoms. The authors explore the biological mechanisms that might explain why some patients develop chronic muscle fatigue and brain fog after viral illness, and compare these processes to ME/CFS. This research suggests that multiple different viruses may cause fatigue through similar pathways in the body.

E3 PreliminaryReviewPEM requiredReview-Narrative

[Myalgic Encephalitis/Chronic Fatigue Syndrome: Diagnostic and Therapeutic Approach and Biological Research].

Sato, Wakiro·Brain and nerve = Shinkei kenkyu no shinpo·2023

This article reviews what we currently know about ME/CFS, a serious illness marked by extreme tiredness, sleep problems, difficulty thinking clearly, and difficulty standing up without symptoms getting worse. A key feature is post-exertional malaise—when patients feel much worse after physical or mental activity—which means people with ME/CFS need to carefully manage their activity levels. The article summarizes current approaches to diagnosis and treatment, as well as recent scientific discoveries about what happens in the body during this disease.

Energy MetabolismPost-Exertional Malaise

Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients.

Glass, Katherine A, Germain, Arnaud, Huang, Yuhsin V et al.·International journal of molecular sciences·2023

Researchers tested urine samples from ME/CFS patients and healthy people before and after intense exercise. They found that healthy people's urine chemistry changed noticeably after exercise (showing normal recovery), but ME/CFS patients' urine chemistry barely changed. This suggests that ME/CFS patients' bodies may not be adapting properly to physical stress the way healthy bodies do.

E3 PreliminaryCohortPEM requiredCase-Control

A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level.

Jinushi, Ryuhei, Nishiguchi, Sho, Masuda, Sakue et al.·Clinical case reports·2023

This study describes a patient who developed ME/CFS after recovering from COVID-19. The researchers found that this patient had lower-than-normal levels of acylcarnitine, a substance the body uses to produce energy. The study reviews existing research on how COVID-19 can lead to ME/CFS, a condition that causes severe fatigue and symptoms that worsen after physical activity.

BiomarkersPost-Exertional Malaise

E3 PreliminaryMechanismPEM unclearMechanistic

Suppressed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome.

Uhde, Melanie, Indart, Alyssa C, Green, Peter H R et al.·Brain, behavior, & immunity - health·2023

This study found that people with ME/CFS have a weakened immune response to bacteria that leak through a damaged gut lining, along with unusual changes in how their bodies process glucose and other nutrients. The immune system appears to be suppressed in some ways while overactive in others, and these patterns were linked to metabolic changes. These findings suggest that gut health and metabolic dysfunction may play important roles in ME/CFS symptoms.

Energy MetabolismImmune SystemPost-Exertional Malaise

E3 PreliminaryGuidelinePEM requiredGuideline

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Adolescents: Practical Guidance and Management Challenges.

Rowe, Katherine·Adolescent health, medicine and therapeutics·2023

ME/CFS is a serious illness causing extreme tiredness that doesn't improve with rest, along with worsening after activity, brain fog, poor sleep, and sometimes dizziness and pain. This paper reviews what we know about treating ME/CFS in teenagers and young people, finding that currently there are no proven cure treatments, but symptom management and lifestyle adjustments help most. The study emphasizes that staying connected to school and having supportive doctors who listen made the biggest difference in how well young people managed their illness over time.