Evidence browser

Hypothetical framework for post-COVID 19 condition based on a fibromyalgia pathogenetic model.

Martínez-Lavín, Manuel, Miguel-Álvarez, Adriana·Clinical rheumatology·2023

This study compares three conditions that share similar symptoms: fibromyalgia, ME/CFS, and long COVID. All three cause fatigue, brain fog, and widespread pain. Researchers propose that these conditions may work through the same biological mechanism—specifically, problems with nerve fiber communication in the body—and suggest that long COVID may develop through the same pathway as fibromyalgia.

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.

Whole-body cryotherapy as a treatment for chronic medical conditions?

Tabisz, Hanna, Modlinska, Aleksandra, Kujawski, Sławomir et al.·British medical bulletin·2023

This review article examines whole-body cryotherapy (WBC)—exposing your entire body to very cold temperatures—as a possible treatment for various chronic conditions, including ME/CFS. The authors suggest that because WBC appears to reduce inflammation in the body, it might help conditions involving persistent inflammation. However, they emphasize that current research quality is low and that proper clinical trials are needed before we can know if WBC actually works.

E3 PreliminaryReviewPEM requiredReview-Narrative

A review of cytokine-based pathophysiology of Long COVID symptoms.

Low, Russell N, Low, Ryan J, Akrami, Athena·Frontiers in medicine·2023

This review examines how Long COVID may develop through a chain reaction of immune system problems. When the virus infects the body, it can trigger ongoing inflammation that affects both the immune system and the brain, potentially causing blood clots in small vessels. This combination may explain symptoms like fatigue, brain fog, and pain that Long COVID and ME/CFS patients experience.

NeuroinflammationPost-Exertional Malaise

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.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome.

Li, Bin-Bin, Feng, Chu-Wen, Qu, Yuan-Yuan et al.·World journal of acupuncture-moxibustion·2023

This review examined how ME/CFS affects the brain and nervous system by looking at laboratory tests and brain imaging studies. Researchers found that people with ME/CFS have changes in brain structure, abnormal inflammation, and problems with chemical messengers in the brain. The study also explored how acupuncture might help correct some of these brain abnormalities in animal models of the condition.

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Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome.

Maes, Michael, Kubera, Marta, Kotańska, Magdalena·Frontiers in psychiatry·2022

This study examined proteins and metabolites in ME/CFS patients to understand how the disease works at a molecular level. Researchers found that ME/CFS involves problems with three interconnected cellular systems: how cells handle harmful oxidative stress, how the immune system responds through inflammation, and how cells communicate through a pathway called Wnt/β-catenin. The study suggests ME/CFS may be triggered by various causes—like infections or toxic exposures—but they all damage these same three systems.

NeuroinflammationImmune SystemPost-Exertional Malaise

Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses.

Tate, Warren, Walker, Max, Sweetman, Eiren et al.·Frontiers in neurology·2022

This study explores why ME/CFS and Long COVID symptoms persist and come and go in cycles. The researchers propose that after an initial trigger—like a viral infection, chemical exposure, or major stress—inflammation spreads to the brain through damaged blood vessels, causing ongoing brain inflammation that keeps the illness cycling. They suggest that similar mechanisms may explain why both ME/CFS (from various causes) and Long COVID (from COVID-19) produce remarkably similar symptoms despite different starting triggers.

E3 PreliminaryMechanismPEM unclearMechanistic

Tissue specific signature of HHV-6 infection in ME/CFS.

Kasimir, Francesca, Toomey, Danny, Liu, Zheng et al.·Frontiers in molecular biosciences·2022

This study looked for signs of active HHV-6 virus (a common herpesvirus) in brain and spinal cord tissue from ME/CFS patients after death, compared to people without ME/CFS. Using a special detection technique, researchers found markers of active viral infection in the nervous tissue of ME/CFS patients but not in the control group. This suggests that HHV-6 may be reactivating specifically in the brain and nervous system in ME/CFS, rather than in the blood where it's usually tested.

E3 PreliminaryMechanismPEM requiredMechanistic

Exosome-associated mitochondrial DNA from patients with myalgic encephalomyelitis/chronic fatigue syndrome stimulates human microglia to release IL-1β.

Tsilioni, Irene, Natelson, Benjamin, Theoharides, Theoharis C·The European journal of neuroscience·2022

This study found that after exercise, patients with ME/CFS have more pieces of DNA from their mitochondria (the energy-producing parts of cells) floating in their blood inside tiny particles called exosomes. When researchers tested these exosomes on immune cells in the lab, they triggered the release of IL-1β, a chemical that causes inflammation in the brain. This suggests that exercise might trigger a chain reaction involving these DNA-carrying particles that could contribute to ME/CFS symptoms.

NeuroinflammationImmune SystemPost-Exertional Malaise

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 PreliminaryMechanismPEM not requiredMechanistic

Differential Impacts of HHV-6A versus HHV-6B Infection in Differentiated Human Neural Stem Cells.

Bahramian, Elham, Furr, Mercede, Wu, Jerry T et al.·Frontiers in immunology·2022

This study examined how two closely related viruses called HHV-6A and HHV-6B infect different types of nerve cells in the brain. Researchers found that both viruses can infect certain brain cells that use glutamate and dopamine (chemical messengers), but neither virus infected a third type of brain cell that uses GABA. Importantly, HHV-6A appeared to cause more damage to infected cells than HHV-6B, suggesting it may be more harmful to nerve tissue.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

No Signs of Neuroinflammation in Women With Chronic Fatigue Syndrome or Q Fever Fatigue Syndrome Using the TSPO Ligand [11C]-PK11195.

Raijmakers, Ruud, Roerink, Megan, Keijmel, Stephan et al.·Neurology(R) neuroimmunology & neuroinflammation·2022

Researchers used a specialized brain scan to look for signs of inflammation in the brains of women with ME/CFS and Q fever fatigue syndrome, compared to healthy women. The scan didn't find evidence of the type of brain inflammation they were looking for, which contradicts some earlier research suggesting inflammation might play a role in these conditions.

NeuroinflammationBiomarkersImmune System

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Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE).

Gottschalk, Gunnar, Peterson, Daniel, Knox, Konstance et al.·Molecular and cellular neurosciences·2022

Researchers found that people with ME/CFS have higher levels of a protein called ATG13 in their blood compared to healthy people. When they tested this protein on brain immune cells in the lab, it triggered the production of harmful molecules called free radicals (oxidative stress). This suggests that a breakdown in the body's cellular recycling system (autophagy) might contribute to the inflammation and stress response seen in ME/CFS.

At the Root of 3 "Long" Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome.

James, Lisa M, Georgopoulos, Apostolos P·Neuroscience insights·2022

This review explores why some people develop long-lasting illnesses after exposure to viruses or bacteria, while others recover normally. The researchers propose that certain infections may persist in the body longer in people with specific immune system markers (HLA types), potentially causing ongoing damage to the brain and other organs. They suggest this mechanism might explain symptoms seen in ME/CFS, long-COVID, and Gulf War Illness.

Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features.

Mohamed, Mohamed S, Johansson, Anton, Jonsson, Jörgen et al.·International journal of molecular sciences·2022

This study reviews how the virus that causes COVID-19 may damage the nervous system and brain, leading to long-term symptoms similar to those seen in other coronavirus outbreaks. The authors identify specific brain mechanisms—involving inflammation, nerve cell communication problems, and hormone regulation—that could explain why some people develop persistent neurological symptoms after COVID-19. These findings suggest potential targets for future treatments.

Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation?

Sun, Yuanjie, Koyama, Yoshihisa, Shimada, Shoichi·Frontiers in aging neuroscience·2022

This review explores how inflammation in the body's organs—like the gut, lungs, or joints—can trigger inflammation in the brain. The authors describe several pathways by which this happens, including damage to the protective barrier around the brain, activation of immune cells in the brain, and communication through nerves connecting organs to the brain. ME/CFS is highlighted as one disease where this peripheral-to-brain inflammation mechanism may be important.

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Stellate ganglion block reduces symptoms of Long COVID: A case series.

Liu, Luke D, Duricka, Deborah L·Journal of neuroimmunology·2022

This small study looked at a procedure called a stellate ganglion block, which uses local anesthetic to temporarily quiet the nerve signals in the neck that control your 'fight or flight' response. Two Long COVID patients received this procedure, and their symptoms—including fatigue, brain fog, and dizziness upon standing—improved. The authors suggest that an imbalance in the autonomic nervous system (the system that controls automatic body functions) may be contributing to Long COVID symptoms.