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Associations Between Psychological and Immunological Variables in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review.

Raanes, Emilie F W, Stiles, Tore C·Frontiers in psychiatry·2021

This review looked at 14 studies to understand how the mind and immune system are connected in ME/CFS. Researchers found that psychological factors like sleep quality, how people manage emotions, and how well they interact with others were linked to immune markers called cytokines. While these connections exist, the evidence is still limited and most studies were done at single points in time rather than following patients over years.

NeuroinflammationImmune System

The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.

Moghimi, Narges, Di Napoli, Mario, Biller, José et al.·Current neurology and neuroscience reports·2021

This review examined what we know about how COVID-19 can affect the nervous system in people who experience long-term symptoms after infection (called PASC or long COVID). The researchers looked at published studies to understand how common these neurological problems are, who is most at risk, why they happen, and how they might be treated. They found that long COVID can range from mild to severely disabling symptoms that last weeks or longer, and that multiple factors—including lingering inflammation, immune system problems, and possible viral effects on the brain—may play a role.

E0 ConsensusReviewPEM requiredReview-Narrative

A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome.

Noor, Nazir, Urits, Ivan, Degueure, Arielle et al.·Anesthesiology and pain medicine·2021

This review summarizes what researchers currently understand about ME/CFS, a complex illness causing severe fatigue and other symptoms. The condition may involve problems with the immune system, stress response, or nervous system, and can be triggered by infections like Epstein-Barr virus, though not always. Diagnosis requires six months of fatigue plus four symptoms like memory problems, sore throat, or post-exertion malaise, and doctors must rule out other conditions first. Treatment options include therapy, medication, and newer approaches like electrical stimulation, though more research is needed to find the best approaches.

SleepImmune SystemPost-Exertional Malaise

Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Brownlie, Helen, Speight, Nigel·Healthcare (Basel, Switzerland)·2021

This review examined past studies on intravenous immunoglobulin (IV IgG), a blood-based treatment, for ME/CFS. The authors found that while results were previously thought to be mixed, a closer look suggests IV IgG may actually help a meaningful group of patients—particularly those with severe ME/CFS who have specific immune system markers. Some patients experienced temporary worsening of symptoms like headaches during treatment, which may actually indicate the treatment was working rather than causing harm.

E0 ConsensusReviewPEM unclearMeta-Analysis

The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data.

Malato, João, Sotzny, Franziska, Bauer, Sandra et al.·Heliyon·2021

This study looked at whether people with ME/CFS have lower levels of a protein called ACE2, which the COVID-19 virus uses to enter cells. The researchers analyzed existing genetic data from ME/CFS patients and found that ACE2 levels were indeed reduced in ME/CFS patients compared to healthy people. The authors suggest this may put ME/CFS patients at higher risk for severe COVID-19 and recommend they be prioritized for vaccination.

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms.

Proal, Amy D, VanElzakker, Michael B·Frontiers in microbiology·2021

Some people who recover from COVID-19 infection continue to experience symptoms for months afterward, a condition called Long COVID or PASC. This review examines multiple biological explanations for why this happens, including organ damage, lingering virus in the body, reactivation of dormant viruses, immune system dysfunction, blood clotting problems, and the body's own immune cells attacking healthy tissues. The authors suggest that different patients likely have different underlying causes, which means different treatments may work best for different people.

E0 ConsensusReviewPEM unclearEditorial

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!

Ariza, Maria Eugenia·Biomolecules·2021

This review examines whether certain viruses, particularly Epstein-Barr virus (EBV), may play a role in ME/CFS. Earlier research on this topic produced mixed results, leading some scientists to think viruses weren't involved. However, newer research methods have found that specific proteins made by EBV could contribute to immune system and nervous system problems in some ME/CFS patients.

New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice.

Froghi, Saied, Grant, Charlotte R, Tandon, Radhika et al.·Clinical reviews in allergy & immunology·2021

This review examines how calcium moves into cells through special channels called TRP channels, and how this process affects the immune system. The authors explain that TRP channels play important roles in helping immune cells fight infections and respond to threats. They discuss evidence that problems with these calcium channels may be involved in several diseases, including ME/CFS.

E0 ConsensusReviewPEM not requiredReview-Narrative

Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments.

Yong, Shin Jie·Infectious diseases (London, England)·2021

This review examines what we know about Long COVID, an illness that affects some people after they recover from COVID-19 infection. The main symptoms are extreme tiredness and breathing difficulties that last for months, along with brain fog, pain, and heart problems. Researchers found that Long COVID may be caused by lasting damage to organs like the lungs and brain, combined with ongoing inflammation in the body.

Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome.

Ruiz-Pablos, Manuel, Paiva, Bruno, Montero-Mateo, Rosario et al.·Frontiers in immunology·2021

This review examines whether Epstein-Barr virus (EBV), a common virus that causes mononucleosis, might play a role in causing ME/CFS in some patients. The researchers found that certain people may have genetic traits that make them more vulnerable to EBV, and in these individuals, the virus might hide from the immune system in a way that leads to ME/CFS symptoms. They suggest that antiviral treatments targeting EBV could potentially help some ME/CFS patients.

E0 ConsensusReviewPEM not requiredReview-Narrative

Complex syndromes of chronic pain, fatigue and cognitive impairment linked to autoimmune dysautonomia and small fiber neuropathy.

Shoenfeld, Yehuda, Ryabkova, Varvara A, Scheibenbogen, Carmen et al.·Clinical immunology (Orlando, Fla.)·2020

This review brings together evidence suggesting that ME/CFS, along with related conditions like POTS and complex regional pain syndrome, may share a common autoimmune root cause. The researchers found that these conditions are linked by similar patterns: the body's immune system produces antibodies that attack certain nerve receptors, and small nerve fibers become damaged. By understanding these shared mechanisms, doctors may eventually be able to better identify which patients would benefit from immune-targeting treatments.

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome.

Bjørklund, Geir, Dadar, Maryam, Pivina, Lyudmila et al.·Molecular neurobiology·2020

This review looked at how ME/CFS develops by examining immune system problems, oxidative stress (cellular damage from harmful molecules), infections, and nutritional issues. Researchers found that people with ME/CFS often have changes in their immune cells and proteins, along with signs of cellular damage that could explain fatigue, pain, and other symptoms. The study suggests that treatments targeting oxidative stress and nutrition might help, though more research is needed.

Gulf war illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis. Similar disabling conditions possibly linked to vaccine-induced autoimmune dysautonomia.

Martinez-Lavin, Manuel, Tejada-Ruiz, Melina·Autoimmunity reviews·2020

This review looked at three conditions that share similar symptoms—Gulf War illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis—and found they may have a common cause related to vaccines. All three conditions involve chronic fatigue, widespread pain, and cognitive problems. The authors propose that in some susceptible people, vaccines or multiple vaccines given close together might trigger an autoimmune reaction affecting the nervous system that controls heart rate, blood pressure, and other automatic body functions.

E0 ConsensusReviewPEM not requiredSystematic-Review

The clinical value of cytokines in chronic fatigue syndrome.

Yang, Tiansong, Yang, Yan, Wang, Delong et al.·Journal of translational medicine·2019

This review examined whether immune system signaling molecules called cytokines could help doctors diagnose or treat ME/CFS. While researchers found that cytokines are abnormal in ME/CFS patients' blood and fluid around the brain, the current evidence shows these markers are not reliable enough to use alone for diagnosis. The review suggests that measuring multiple cytokines together might help doctors better understand what's happening in individual patients, but cytokines are not yet proven as effective treatment targets.

E0 ConsensusReviewPEM not requiredReview-Narrative

Shared microglial mechanisms underpinning depression and chronic fatigue syndrome and their comorbidities.

Chaves-Filho, Adriano José Maia, Macedo, Danielle S, de Lucena, David Freitas et al.·Behavioural brain research·2019

This review examined how depression and ME/CFS might share common causes in the brain, specifically through immune cells called microglia. Researchers found that when these brain immune cells become overactive, they may trigger both depression and the fatigue characteristic of ME/CFS. The study suggests that reducing this immune activation could potentially help treat both conditions.

NeuroinflammationImmune System

E0 ConsensusReviewPEM not requiredMeta-Analysis

Inflammatory proteins are altered in chronic fatigue syndrome-A systematic review and meta-analysis.

Strawbridge, Rebecca, Sartor, Maria-Laura, Scott, Fraser et al.·Neuroscience and biobehavioral reviews·2019

This research review looked at 42 studies measuring inflammatory proteins (substances in the blood linked to inflammation) in people with ME/CFS compared to healthy people. The researchers found that people with ME/CFS had higher levels of five specific inflammatory proteins, but twelve other proteins were similar to healthy controls. This suggests that inflammation may play a role in ME/CFS for some patients, but it's likely not the main problem for everyone with the condition.

E0 ConsensusReviewPEM requiredReview-Narrative

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Missailidis, Daniel, Annesley, Sarah J, Fisher, Paul R·Diagnostics (Basel, Switzerland)·2019

ME/CFS is a complex condition affecting multiple body systems, and researchers are working to understand what causes it. This review shows that evidence points to problems in the immune system, nervous system, muscle function, metabolism, and gut health in ME/CFS patients. Because patients experience different symptoms and may develop the condition in different ways, finding reliable diagnostic tests remains a key challenge that researchers are actively pursuing.

A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis/chronic fatigue syndrome.

Eaton-Fitch, Natalie, du Preez, Stanley, Cabanas, Hélène et al.·Systematic reviews·2019

This review examined research on natural killer cells, which are immune cells that help fight infections and abnormal cells in the body. Scientists found that people with ME/CFS consistently have natural killer cells that don't work as well as they should. This discovery was the most reliable and consistent finding across all the studies reviewed, suggesting it could be an important marker for understanding ME/CFS.

Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation.

Almenar-Pérez, Eloy, Ovejero, Tamara, Sánchez-Fito, Teresa et al.·Clinical therapeutics·2019

This study reviewed research on how ME/CFS may involve changes in how genes are regulated, not the genes themselves. The researchers discovered that dormant DNA sequences called transposable elements—which make up almost half of our genome and were previously thought to be 'junk DNA'—might become activated in ME/CFS patients. This activation could trigger the immune system to attack without an actual infection present.

A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID).

Corbitt, Matthew, Eaton-Fitch, Natalie, Staines, Donald et al.·BMC neurology·2019

Researchers reviewed 15 studies that measured immune signaling molecules called cytokines in people with ME/CFS compared to healthy people. Although many studies have looked at cytokines in ME/CFS, the results were too mixed and inconsistent to show that cytokines could be used as a reliable test for the condition or to confirm a clear role in causing the disease.