Evidence browser

E3 PreliminaryMechanismPEM not requiredMechanistic

Reducing fatigue-related symptoms in Long COVID-19: a preliminary report of a lymphatic drainage intervention.

Heald, Adrian, Perrin, Raymond, Walther, Andreas et al.·Cardiovascular endocrinology & metabolism·2022

This small study looked at whether a hands-on technique called the Perrin technique—involving gentle massage and movement exercises—could help reduce fatigue in people with Long COVID. Twenty patients received weekly treatment sessions and did daily self-massage at home. On average, both men and women reported about 50% improvement in their fatigue-related symptoms after treatment. While these early results are encouraging, the study is too small to prove this treatment works for everyone.

Study on the active components and mechanism of Suanzaoren decoction in improving cognitive impairment caused by sleep deprivation.

Cheng, Li, Wang, Fei, Li, Zi-Heng et al.·Journal of ethnopharmacology·2022

This study examined how an ancient Chinese herbal remedy called Suanzaoren Decoction (SZRD) might help improve thinking and memory problems caused by poor sleep. Researchers used computer analysis and laboratory experiments to identify the active ingredients in the herbs and understand how they work in the body, finding that the remedy may work through pathways related to estrogen in the brain.

SleepCognitive Impairment

NeuroinflammationImmune System

The Role of Neuro-Immune Interaction in Chronic Pain Conditions; Functional Somatic Syndrome, Neurogenic Inflammation, and Peripheral Neuropathy.

Meade, Elaine, Garvey, Mary·International journal of molecular sciences·2022

This review article examines how the nervous and immune systems interact to cause chronic pain and fatigue in conditions like ME/CFS, fibromyalgia, and IBS. The authors explain that childhood trauma and ongoing stress can permanently change how the body's stress response system works, leading to long-term symptoms. They discuss how these systems become dysregulated and contribute to the wide range of symptoms people with these conditions experience.

E3 PreliminaryCommentaryPEM requiredEditorial

[Post-COVID syndrome with fatigue and exercise intolerance: myalgic encephalomyelitis/chronic fatigue syndrome].

Renz-Polster, Herbert, Scheibenbogen, Carmen·Innere Medizin (Heidelberg, Germany)·2022

This article explains that ME/CFS is a serious neurological and immune system disease, often triggered by infections like COVID-19, characterized by extreme fatigue lasting at least 6 months and a unique symptom called post-exertional malaise (PEM)—where even mild activity causes symptoms to worsen hours or days later. The authors stress that ME/CFS is a distinct medical condition that should not be confused with ordinary tiredness, and while there is no cure yet, treatment focuses on managing symptoms, addressing related circulation problems, and helping patients conserve energy through pacing.

E3 PreliminaryMechanismPEM unclearLongitudinal

Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Helliwell, Amber M, Stockwell, Peter A, Edgar, Christina D et al.·International journal of molecular sciences·2022

This study looked at how a person's DNA changes during ME/CFS relapses by examining two patients' genetic material multiple times over several months as they experienced a relapse and recovery. The researchers found that during relapses, the patients' DNA showed much larger changes in a process called methylation (a chemical marking system that controls which genes are active) compared to healthy people. These changes affected genes involved in metabolism, immune function, and inflammation—processes that are important in ME/CFS.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Estimating total morbidity burden of COVID-19: relative importance of death and disability.

Smith, Maia P·Journal of clinical epidemiology·2022

This study looked at the total health impact of COVID-19 by measuring not just deaths, but also the years of healthy life lost due to long-COVID symptoms. The researchers found that most of the burden from COVID-19 actually comes from people who survive but live with ongoing disability—not from deaths alone. The study suggests that resources should focus on preventing and treating long-COVID, especially in younger people and women who appear to bear a larger share of this burden.

The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Dehhaghi, Mona, Panahi, Hamed Kazemi Shariat, Kavyani, Bahar et al.·Aging and disease·2022

This review examines how tryptophan, an amino acid we get from food, is processed differently in people with ME/CFS. The body normally converts tryptophan into important substances like serotonin (which affects mood) and NAD+, an energy molecule. The authors propose that this conversion process may become overactive in ME/CFS, depleting NAD+ and making fatigue worse. They suggest that NAD+ supplements might help reduce fatigue and improve quality of life.

E3 PreliminaryBehavioralPEM not requiredObservational

Can l-carnitine reduce post-COVID-19 fatigue?

Vaziri-Harami, Roya, Delkash, Parisa·Annals of medicine and surgery (2012)·2022

Some people develop long-lasting fatigue after COVID-19 infection, similar to ME/CFS, and this fatigue can last for months. This article suggests that L-carnitine, a natural substance that helps cells produce energy, might help reduce this type of fatigue based on its success in treating fatigue caused by other diseases like cancer and multiple sclerosis. The authors recommend testing L-carnitine in clinical trials to see if it actually works and is safe for people with post-COVID fatigue.

Interventions

Mechanism of the Huangguoshu waterfall forest environment's promotive effect on human health in Guizhou, China.

Zhu, Zixin, Zhao, Xueke, Ouyang, Qiuyue et al.·Annals of translational medicine·2022

This study looked at whether spending time in a waterfall forest environment in China could help people with ME/CFS feel better. Researchers tracked what participants looked at, measured their fatigue and mood, and checked blood markers for inflammation and antioxidants. They found that people who spent time near the waterfall had less fatigue and depression, lower inflammation, and higher antioxidant levels.

E3 PreliminaryMechanismPEM requiredMechanistic

Differential Effects of Exercise on fMRI of the Midbrain Ascending Arousal Network Nuclei in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) in a Model of Postexertional Malaise (PEM).

Baraniuk, James N, Amar, Alison, Pepermitwala, Haris et al.·Brain sciences·2022

This study used brain imaging to examine how exercise affects people with ME/CFS and Gulf War Illness. Researchers found that after exercise, the brains of ME/CFS patients showed increased activity in areas that control alertness, mood, pain, and sleep, while Gulf War Illness patients showed the opposite pattern (decreased activity). These findings suggest that ME/CFS and Gulf War Illness affect the brain differently, which may explain why exercise can make symptoms worse in ME/CFS patients.

E3 PreliminaryMechanismPEM unclearMechanistic

EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.

Cox, Brandon S, Alharshawi, Khaled, Mena-Palomo, Irene et al.·JCI insight·2022

This study found that some people with ME/CFS have abnormal immune responses linked to past infections with Epstein-Barr virus (EBV) and human herpesvirus 6A (HHV-6A). The researchers discovered that proteins from these viruses may trigger the immune system to produce excess amounts of certain signaling molecules, leading to confused immune cell behavior. This suggests a possible biological mechanism for how these common viruses might contribute to ME/CFS symptoms in some patients.

Immune System

Immune SystemPost-Exertional Malaise

Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19.

McCarthy, Michael J·Brain, behavior, & immunity - health·2022

This review examines whether disrupted body clocks (circadian rhythms) contribute to ME/CFS symptoms like fatigue, sleep problems, and cognitive difficulties. The authors focus on a specific immune molecule called TGFB that may interfere with the body's natural daily rhythms. They suggest that COVID-19 infections may cause similar circadian disruptions, potentially explaining why some people develop long COVID symptoms that resemble ME/CFS.

[Fatigue Doesn't Always have to be caused by SARS-CoV-2: Case Report].

Howanietz, Helmuth, Graf, Ulrike, Kainz, Theresa·Padiatrie und Padologie·2022

This case report describes a 17-year-old girl who experienced severe fatigue caused by Epstein-Barr virus (EBV) infection, commonly known as infectious mononucleosis. The authors highlight that fatigue in young people can come from many different causes, not just COVID-19, and that it's important to identify the correct cause. Notably, about 13.5% of people who have EBV infection go on to develop ME/CFS, making proper diagnosis essential.

Diagnostics

E3 PreliminaryPEM not required

Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability?

Rusin, Andrej, Seymour, Colin, Cocchetto, Alan et al.·International journal of molecular sciences·2022

This review compares ME/CFS with cancer-related fatigue, two conditions that share similar exhaustion symptoms. The authors examined research showing that both conditions may involve problems with stress hormones, immune system inflammation, energy production in cells, and genetic factors. They suggest these two different diseases might actually represent different points on a spectrum of how the body responds to stress, rather than being completely separate conditions.

Energy Metabolism

An Unexpected Journey: The Lived Experiences of Patients with Long-Term Cognitive Sequelae After Recovering from COVID-19.

Loft, Mia I, Foged, Eva M, Koreska, Mai·Qualitative health research·2022

This study listened to people who experienced long-lasting thinking and memory problems after recovering from COVID-19. Patients described how these cognitive symptoms disrupted their daily lives, work, and relationships, and left them feeling anxious and uncertain about their future. The researchers suggest that doctors and researchers could learn from how people with similar conditions—like ME/CFS—manage their symptoms while waiting for treatments.

Cognitive Impairment

Characterising DSCATT: A case series of Australian patients with debilitating symptom complexes attributed to ticks.

Schnall, Jesse, Oliver, Georgina, Braat, Sabine et al.·The Australian and New Zealand journal of psychiatry·2022

Researchers studied 29 Australian patients who believed their symptoms were caused by tick bites. Most had severe tiredness, headaches, and joint pain, and many had previously been diagnosed with conditions like ME/CFS or fibromyalgia. When doctors tested these patients, they found no evidence of Lyme disease or other common infections from ticks. The study suggests that tick-attributed illness in Australia remains unexplained and may overlap with other medically unexplained conditions.

Diagnostics

Immune SystemLong COVID Overlap

New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition.

Gavrilova, Natalia, Soprun, Lidiia, Lukashenko, Maria et al.·Pathophysiology : the official journal of the International Society for Pathophysiology·2022

This study describes a pattern found in some people who developed fibromyalgia (widespread pain) after COVID-19 infection. The researchers noticed that young women with loose, flexible joints who had COVID-19 and a specific tendon injury were more likely to develop fibromyalgia along with signs of inflammation. The study presents three patient cases that fit this pattern, suggesting COVID-19 may trigger fibromyalgia in people whose connective tissues are already prone to damage.

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Evaluation of natural killer cell assay performance on shipped blood specimens.

Querec, Troy D, Abrams, Joseph, Stewart, Jennifer J et al.·Journal of immunological methods·2021

This study tested different laboratory methods for measuring natural killer (NK) cell function—an immune system measurement that may be important for ME/CFS—using blood samples that were shipped overnight instead of tested immediately. Researchers compared three different testing approaches and found that two of them (CRCA and FCCA) gave similar results when blood samples were processed a day after collection, suggesting these tests could work for clinical settings where samples need to be shipped.

BiomarkersImmune System