Evidence browser

NeuroinflammationPost-Exertional Malaise

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.

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Myalgic Encephalomyelitis-Chronic Fatigue Syndrome Common Data Element item content analysis.

Slavin, Mary D, Bailey, Hannah M, Hickey, Emily J et al.·PloS one·2023

This study examined how well existing questionnaires measure the main symptoms of ME/CFS. Researchers looked at 38 different symptom-assessment tools and found they do a good job measuring physical symptoms like fatigue, sleep problems, and pain. However, most tools don't adequately measure how ME/CFS limits daily activities and participation in work, social life, and other important areas of life.

E3 PreliminaryMechanismPEM requiredMechanistic

Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Maya, Jessica, Leddy, Sabrina M, Gottschalk, C Gunnar et al.·International journal of molecular sciences·2023

Researchers studied immune cells called lymphocytes from ME/CFS patients and found that these cells use fatty acids (a type of fuel) differently than healthy people's immune cells do. When immune cells are activated or working hard, ME/CFS patients' cells rely more heavily on burning fat for energy compared to cells from healthy controls. This suggests that ME/CFS patients' immune systems may have a fundamental problem with how they fuel their cells.

Energy MetabolismImmune SystemPost-Exertional Malaise

Post-COVID and ME/CFS - DoWe Need New Disease Theories?

Schauenburg, Henning·Zeitschrift fur Psychosomatische Medizin und Psychotherapie·2023

This review examines how post-COVID illness and ME/CFS develop and persist, looking beyond just physical symptoms to understand how the brain perceives and responds to the body. The authors suggest that standard medical tests only partially explain chronic fatigue, and that a newer theory called 'Predictive Coding' may help us understand how the mind and body interact in these complex conditions. The goal is to develop better treatments while avoiding the harmful stigma of labeling these as 'just psychological' problems.

E3 PreliminaryDiagnosticPEM requiredPreprintPreprint

A Mixed Methods System for the Assessment of Post Exertional Malaise in Encephalomyelitis/Chronic Fatigue Syndrome.

Stussman, Barbara, Calco, Brice, Norato, Gina et al.·medRxiv : the preprint server for health sciences·2023

This study looked at how to better measure post-exertional malaise (PEM)—the symptom flare-up that happens after activity in ME/CFS patients. Researchers asked 10 ME/CFS patients and 9 healthy people to do an exercise test, then tracked their symptoms over 72 hours using both rating scales and detailed interviews. They found that combining interviews with rating scales captured PEM patterns much better than rating scales alone, especially because rating scales sometimes hit their limits and couldn't show the full picture of symptom changes.

E3 PreliminaryCohortPEM unclearCase-Control

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: First Described Complication after Gam-COVID-Vac Vaccine.

Manysheva, Ksenia, Sherman, Mikhail, Zhukova, Natalia et al.·Psychiatria Danubina·2022

This report describes one case of a 25-year-old woman who developed ME/CFS symptoms about 10 days after receiving the Sputnik V COVID-19 vaccine. She experienced severe fatigue, muscle pain, and difficulty moving. This is the first documented case linking ME/CFS to this particular vaccine, though it remains unclear whether the vaccine caused the condition or if it occurred by coincidence.

Immune SystemPost-Exertional Malaise

E3 PreliminaryCommentaryPEM required

Letter: Could endothelial dysfunction and vascular damage contribute to pain, inflammation and post-exertional malaise in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)?

Lubell, Jeffrey·Journal of translational medicine·2022

This editorial letter explores whether problems with blood vessel function and damage might explain some of the key symptoms of ME/CFS, including pain, inflammation, and post-exertional malaise (the exhaustion that follows physical activity). The author proposes that if blood vessels aren't working properly, they may not deliver enough oxygen and nutrients to tissues, which could trigger the symptoms many ME/CFS patients experience.

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.

The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications.

Kell, Douglas B, Pretorius, Etheresia·The Biochemical journal·2022

This paper proposes that ME/CFS, Long COVID, and some other chronic diseases may be caused by a harmful cycle involving tiny blood clots blocking small blood vessels, followed by damage when blood flow returns. The authors suggest that this process creates harmful molecules called free radicals and triggers inflammation and other problems. They review existing evidence that treatments like antioxidants, anti-inflammatory drugs, and blood thinners might help address these underlying mechanisms.

E3 PreliminaryCommentaryPEM requiredEditorial

[Facts and myths about chronic fatigue syndrome].

Fink, Per, Skjernov, Mathias, Petersen, Line Kirkeby et al.·Ugeskrift for laeger·2022

This article discusses updates to ME/CFS treatment guidelines and challenges some common beliefs about the condition. The authors argue that new guidelines recommend against intense exercise programs for severely ill patients and suggest energy management instead, but they question whether the evidence supporting these changes was properly evaluated. They raise concerns about how the new guidelines were developed and what type of evidence was considered.

Severe MEPost-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19.

Soares, Madu N, Eggelbusch, Moritz, Naddaf, Elie et al.·Journal of cachexia, sarcopenia and muscle·2022

Many people with COVID-19 and long COVID experience muscle weakness and tiredness, especially after physical activity. This review examines what happens inside muscle cells in these patients, including muscle fiber shrinkage, changes in how muscles use energy, and immune cell buildup. The authors suggest that severe illness, lack of activity, low oxygen levels, and poor nutrition all contribute to these problems, similar to what happens in other serious conditions.

NeuroinflammationPost-Exertional Malaise

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure.

Renz-Polster, Herbert, Tremblay, Marie-Eve, Bienzle, Dorothee et al.·Frontiers in cellular neuroscience·2022

This study suggests that ME/CFS might be caused by problems with certain support cells in the brain called glia, which help protect and maintain nerve cells. The researchers reviewed existing research on two key ME/CFS symptoms—feeling worse after activity and reduced blood flow to the brain—and found evidence that brain cell dysfunction could explain many of the different problems seen in ME/CFS.

Energy MetabolismPost-Exertional Malaise

Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach.

Wirth, Klaus J, Scheibenbogen, Carmen·Medicina (Kaunas, Lithuania)·2022

Many people with post-COVID syndrome experience shortness of breath and chest pain, even though their lungs and heart are typically healthy. This study proposes that the problem may stem from overbreathing (hyperventilation) during exercise, combined with problems in how the body regulates breathing and uses energy in muscles. The authors suggest that overbreathing creates a harmful cascade inside cells—disrupting sodium and calcium balance—which worsens fatigue and breathing difficulties. Preventing overbreathing might be a way to help these patients recover.

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.

Cognitive ImpairmentPost-Exertional Malaise

Review of the Midbrain Ascending Arousal Network Nuclei and Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and Postexertional Malaise (PEM).

Baraniuk, James N·Brain sciences·2022

This review examines a brain region called the midbrain and how it might contribute to post-exertional malaise (PEM)—the worsening of symptoms after activity that happens in ME/CFS. When ME/CFS patients did exercise in a study, their midbrain showed increased activity during mental tasks, while Gulf War Illness patients showed the opposite pattern. The authors suggest that problems in this brain region could explain why ME/CFS patients have trouble with energy, sleep, mood, pain, and temperature control, especially after exertion.

Immune SystemPost-Exertional Malaise

The autonomic aspects of the post-COVID19 syndrome.

Dotan, Arad, David, Paula, Arnheim, Dana et al.·Autoimmunity reviews·2022

After COVID-19 infection, many people experience long-lasting symptoms similar to ME/CFS, including fatigue, brain fog, and mood problems. Recent research suggests the immune system may attack nerve cells that control heart rate, blood pressure, and other automatic body functions, rather than just the virus itself. The authors propose that exercise therapy might be safer and more helpful than immunosuppressive drugs for treating these lingering post-COVID symptoms.

E3 PreliminaryCohortPEM unclearCase-Control

Stellate Ganglion Block for Long COVID Symptom Management: A Case Report.

Khan, Mashfee H, Kirkpatrick, Kennedy P, Deng, Yi et al.·Cureus·2022

This study describes one patient with long COVID who received a stellate ganglion block (SGB)—an injection that calms an overactive nervous system. The treatment helped reduce their fatigue, post-exertional malaise (worsening after activity), shortness of breath, and stomach problems. Because the nervous system controls many body functions, blocking specific nerve signals may help relieve symptoms driven by this dysregulation.

Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Stanculescu, Dominic, Bergquist, Jonas·Frontiers in medicine·2022

This paper suggests that ME/CFS might develop through similar biological problems seen in people with severe critical illnesses. The researchers propose that four interconnected issues—reduced blood flow to tissues, damage to the gut lining, problems with pituitary gland function, and low thyroid hormone activity—could work together to create a cycle that keeps ME/CFS going. Understanding these connections could help develop better treatments.

[Long COVID: nosographic aspects and clinical epidemiology].

Abrignani, Maurizio G, Maloberti, Alessandro, Temporelli, Pier Luigi et al.·Giornale italiano di cardiologia (2006)·2022

Long COVID is a condition where people experience ongoing symptoms weeks or months after recovering from COVID-19 infection. Symptoms can include fatigue, difficulty thinking clearly, shortness of breath, muscle pain, sleep problems, and reduced ability to do daily activities. This review looks at how common long COVID is, who is most likely to develop it, and what we currently know about the condition.

Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies.

Yong, Shin Jie, Liu, Shiliang·Reviews in medical virology·2022

This review examines long COVID (persistent symptoms lasting months after COVID-19 infection) and proposes that it comes in six different subtypes, one of which is ME/CFS-like illness. The authors describe the symptoms and potential treatments for each subtype, helping doctors and patients better understand which type of long COVID a person might have. This framework could help lead to more targeted treatments since different subtypes may need different approaches.