Evidence browser

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.

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.

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.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Where will the drugs come from?

Toogood, Peter L, Clauw, Daniel J, Phadke, Sameer et al.·Pharmacological research·2021

ME/CFS is a serious illness causing extreme fatigue that doesn't improve with rest, along with pain, sleep problems, and difficulty thinking clearly. This review looks at what we currently know about ME/CFS, how doctors diagnose it, and what treatments exist today. The authors examined past research to identify promising targets for new medicines that could help treat ME/CFS in the future.

E0 ConsensusReviewPEM unclear

Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Fluge, Øystein, Tronstad, Karl J, Mella, Olav·The Journal of clinical investigation·2021

This review article examines what we know about how ME/CFS damages the body and discusses possible treatments. Researchers looked at existing scientific evidence to understand the disease mechanisms—the biological processes that cause ME/CFS symptoms—and evaluated various interventions that might help patients. The goal was to create a comprehensive overview of current scientific understanding to guide future research and treatment development.

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 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.

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.

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.

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 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.

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.

Fatigue, Sleep, and Autoimmune and Related Disorders.

Zielinski, Mark R, Systrom, David M, Rose, Noel R·Frontiers in immunology·2019

Severe fatigue is one of the most disabling symptoms reported by people with autoimmune diseases, including ME/CFS. This review examines how inflammation and the brain contribute to fatigue in these conditions. The authors explain that fatigue involves multiple body systems—including energy supply, metabolism, mood, and sleep—all of which can be disrupted by inflammation.

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.

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.

E0 ConsensusReviewPEM requiredReview-Narrative

[Myalgic encephalomyelitis or chronic fatigue syndrome].

Brinth, Louise, Nielsen, Henrik, Varming, Kim et al.·Ugeskrift for laeger·2019

ME/CFS is a serious condition that causes extreme tiredness affecting both mind and body, along with pain, sleep problems, difficulty thinking clearly, and a symptom called post-exertional malaise where activity makes symptoms worse. Research has found changes in patients' cells, hormones, immune systems, and how their bodies process energy, which could lead to better ways to diagnose and treat this condition.

BiomarkersEnergy MetabolismImmune SystemPost-Exertional Malaise

The "Biology-First" Hypothesis: Functional disorders may begin and end with biology-A scoping review.

Enck, P, Mazurak, N·Neurogastroenterology and motility·2018

This study reviewed research showing that infections can trigger long-lasting functional disorders—conditions where the body doesn't work properly but standard tests appear normal. The authors propose that these disorders start from biological changes (like immune dysfunction or altered gut bacteria) caused by the infection, and that psychological factors develop as a result rather than being the root cause. This challenges the common belief that such conditions are mainly psychological or social in nature.

Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?

Newberry, Fiona, Hsieh, Shen-Yuan, Wileman, Tom et al.·Clinical science (London, England : 1979)·2018

This review examines whether changes in the bacteria living in our gut and the viruses that affect those bacteria might contribute to ME/CFS. While previous studies have focused mainly on bacterial changes, this paper points out that viruses—especially those that attack bacteria—are equally important to understand. The authors explain that inconsistencies between different microbiome studies make it hard to draw clear conclusions, and call for more standardized research methods.