Evidence browser

Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review.

Helbing, Dario Lucas, Dommaschk, Eva-Maria, Danyeli, Lena Vera et al.·European archives of psychiatry and clinical neuroscience·2024

This review examines whether a natural supplement called acetylcarnitine might help treat long COVID symptoms like fatigue, brain fog, and depression. Acetylcarnitine is a substance your body normally makes that helps cells produce energy. The authors looked at research showing this supplement has helped some people with similar illnesses like ME/CFS and depression, and they propose studying whether it could help long COVID patients too.

Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice.

Wakatsuki, Koji, Kiryu-Seo, Sumiko, Yasui, Masaya et al.·Journal of neuroinflammation·2024

Researchers used mice exposed to repeated cold stress to study how chronic pain develops, similar to fibromyalgia. They found that sensory nerve cells (proprioceptors) become overactive and trigger immune cells in the nervous system called microglia to become inflamed. When they reduced microglial activity with a drug, the pain improved, suggesting that this immune activation along nerve pathways may be a key driver of long-lasting pain.

Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation.

Theoharides, Theoharis C, Twahir, Assma, Kempuraj, Duraisamy·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology·2024

This study examines mast cells, which are immune cells found throughout the body, and how they may be involved in conditions like ME/CFS that affect the nervous system and cause abnormal heart rate and blood pressure responses. Mast cells sit near nerve endings and important organs, where they can release chemicals that affect how the body regulates basic functions like temperature and blood pressure. The researchers suggest that controlling mast cell activation might help treat these conditions, though currently there are no proven treatments.

Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome.

Qu, Yuan-Yuan, Feng, Chu-Wen, Sun, Zhong-Ren et al.·Zhen ci yan jiu = Acupuncture research·2024

Researchers tested whether electroacupuncture—a traditional needle-based treatment—could help rats with experimentally-induced fatigue syndrome. The treated rats showed improved physical endurance, better memory, and reduced anxiety compared to untreated sick rats. The researchers also found that treatment reduced inflammatory markers in the brain and blood that were elevated in sick rats.

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 not requiredReview-Narrative

Role of Tau protein in long COVID and potential therapeutic targets.

Marwaha, Bharat·Frontiers in cellular and infection microbiology·2023

Long COVID causes ongoing fatigue, breathing problems, brain fog, and other symptoms that can last months or years. This review suggests that a protein called tau—which is known to damage the brain in other diseases—may also be involved in Long COVID. The authors propose that future research should look for tau damage in Long COVID patients and that treatments designed to stop tau buildup might help.

NeuroinflammationBiomarkers

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.

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.

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.

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

[Effect of transcutaneous electrical acupoint stimulation on learning and memory ability of chronic fatigue syndrome rats and its mechanisms].

Zhong, Xiao-Ling, Tong, Bo-Ying, Yang, Yi-Han et al.·Zhen ci yan jiu = Acupuncture research·2023

This study tested whether a non-invasive electrical stimulation treatment applied to specific acupuncture points could help rats with chronic fatigue improve their memory and learning. Researchers found that the treatment reduced fatigue symptoms and improved memory performance in fatigued rats, possibly by protecting brain cells in the memory center of the brain.

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.

Perioperative opioid-minimization approach as a useful protocol in the management of patients with Ehlers-Danlos syndrome-hypermobility type, craniocervical instability and severe chronic pain who are to undergo occipito-cervical fixation.

Ramírez-Paesano, Carlos, Rodiera Clarens, Claudia, Sharp Segovia, Allan et al.·Orphanet journal of rare diseases·2023

Some people with Ehlers-Danlos syndrome (a connective tissue disorder) develop neck instability that causes severe pain and fatigue similar to ME/CFS. This review examines how doctors can better manage pain during and after neck surgery in these patients by using less opioid medication and combining multiple pain-relief strategies instead, because opioids often don't work well and can actually make pain worse in these cases.

E3 PreliminaryMechanismPEM unclearMechanistic

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.

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.