Evidence browser

Long COVID: mechanisms, risk factors and recovery.

Astin, Rónan, Banerjee, Amitava, Baker, Mark R et al.·Experimental physiology·2023

This review examines Long COVID—a prolonged illness affecting some people after COVID-19 infection—and compares it to similar post-viral conditions like ME/CFS. Researchers found that Long COVID involves problems with the heart and lungs, muscle function, and how the body regulates its nervous system. The review discusses various treatment approaches being tested, including exercise programs, breathing exercises, and techniques to help calm an overactive nervous system.

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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.

Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases.

Gottschalk, Carl Gunnar, Peterson, Daniel, Armstrong, Jan et al.·Infectious agents and cancer·2023

This review article examines how viral infections—including long COVID, EBV, and others—can trigger severe, lasting fatigue and related symptoms. The authors explore the biological mechanisms that might explain why some patients develop chronic muscle fatigue and brain fog after viral illness, and compare these processes to ME/CFS. This research suggests that multiple different viruses may cause fatigue through similar pathways in the body.

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[Post-COVID Rehabilitation].

Küst, Jutta, Disko, Andreas, Calendo, Luigi Riccardo et al.·Praxis·2023

This guideline explains how to help people recover from post-COVID illness, which can cause lasting fatigue and memory problems that make it hard to work or manage daily life. Since there is no cure yet, treatment focuses on rehabilitation that is tailored to each patient's symptoms and goals, with special attention to gradually rebuilding activity while watching for post-exertional malaise—a worsening of symptoms after physical or mental effort. The approach involves multiple healthcare professionals working together to adjust the workload based on how the patient is doing over time.

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Case report: Rapid improvements of anorexia nervosa and probable myalgic encephalomyelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes.

Hebebrand, Johannes, Antel, Jochen, von Piechowski, Linda et al.·Frontiers in psychiatry·2023

This case report describes a 17-year-old boy who had both anorexia nervosa (an eating disorder) and probable ME/CFS (a condition causing extreme fatigue and pain after exertion). He was treated with a medication called metreleptin for short periods. Notably, the treatment appeared to improve not only his eating disorder symptoms but also his ME/CFS symptoms like fatigue and post-exertional muscle pain. This raises the possibility that metreleptin might help people with ME/CFS, especially those who have also lost significant weight.

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Cardiovascular Considerations in the Management of People With Suspected Long COVID.

Quinn, Kieran L, Lam, Grace Y, Walsh, Jillian F et al.·The Canadian journal of cardiology·2023

This review examines how doctors should evaluate and treat heart-related symptoms in people with long COVID. It highlights that about 15% of Canadians infected with COVID-19 develop persistent symptoms lasting more than 12 weeks, including fatigue, shortness of breath, chest pain, and irregular heartbeats. The authors emphasize that doctors need to consider conditions like ME/CFS, postexertional malaise (symptom flare-ups after activity), and dysautonomia (problems with the autonomic nervous system) when evaluating these patients.

The Long Road of Long COVID: Specific Considerations for the Allergist/Immunologist.

Bellanti, Joseph A, Novak, Peter, Faitelson, Yoram et al.·The journal of allergy and clinical immunology. In practice·2023

Long COVID is a condition that develops after a COVID-19 infection and can cause symptoms affecting many parts of the body, including heart problems, blood clots, fatigue, and autoimmune issues. This review examines what causes Long COVID and which patients are most at risk, noting that certain groups like Hispanic and Latino communities face higher rates. The authors highlight that while vaccines help prevent severe acute COVID, we still need more research to understand how they affect Long COVID development and progression.

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Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Adolescents: Practical Guidance and Management Challenges.

Rowe, Katherine·Adolescent health, medicine and therapeutics·2023

ME/CFS is a serious illness causing extreme tiredness that doesn't improve with rest, along with worsening after activity, brain fog, poor sleep, and sometimes dizziness and pain. This paper reviews what we know about treating ME/CFS in teenagers and young people, finding that currently there are no proven cure treatments, but symptom management and lifestyle adjustments help most. The study emphasizes that staying connected to school and having supportive doctors who listen made the biggest difference in how well young people managed their illness over time.

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My experience with ME/CFS and implications: A personal narrative.

Sirotiak, Zoe·Work (Reading, Mass.)·2023

This article shares the personal story of a young woman who is also a physical therapist and developed ME/CFS after a COVID-19 infection. She describes how the condition dramatically changed her life and how healthcare providers, including rehabilitation specialists, often lack the knowledge needed to properly help ME/CFS patients. The author highlights that ME/CFS remains poorly understood and undertreated, with few proven treatments available.

Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID.

Edward, Justin A, Peruri, Adithya, Rudofker, Eric et al.·Journal of cardiopulmonary rehabilitation and prevention·2023

Long COVID causes severe fatigue and difficulty exercising, affecting 25-30% of people who had COVID-19. This review suggests that carefully designed exercise programs—tailored to avoid making symptoms worse—may help Long COVID patients recover better. The authors argue that much of Long COVID comes from the body becoming deconditioned (out of shape) from inactivity, and that gentle, personalized exercise can help reduce symptoms.

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.

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A patient who recovered from post-COVID myalgic encephalomyelitis/chronic fatigue syndrome: a case report.

Oka, Takakazu·BioPsychoSocial medicine·2023

This case report describes a nurse who developed ME/CFS symptoms after recovering from COVID-19, including severe fatigue, pain, brain fog, and heart palpitations that lasted over 6 months. She received treatment combining dietary advice, supplements, behavioral strategies, exercise conditioning, and two medications (amitriptyline and a Japanese herbal medicine called hochuekkito), and eventually recovered fully and returned to work. This is the first detailed report showing that someone with post-COVID ME/CFS can recover with comprehensive multimodal treatment.

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Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness.

Boruch, Alexander E, Lindheimer, Jacob B, Ninneman, Jacob V et al.·Brain, behavior, & immunity - health·2023

This study looked at whether post-exertional malaise (PEM)—the worsening of symptoms after physical activity—is caused by changes in gene activity in Gulf War illness patients. Veterans with Gulf War illness and healthy controls exercised on stationary bikes, and researchers measured gene expression in blood samples before and after exercise. While the study found that certain genes did change after exercise in Gulf War illness patients, these gene changes did not explain why their symptoms got worse.

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Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles.

Aschman, Tom, Wyler, Emanuel, Baum, Oliver et al.·Acta neuropathologica communications·2023

Researchers examined muscle tissue from people with long COVID who experience fatigue and worsening symptoms after activity. They found that these patients had fewer blood vessels in their muscles, thicker vessel walls, and signs of immune cells that might have been triggered by the initial infection. These physical changes in the muscle's blood supply could explain why exercise makes their symptoms worse.

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Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.

Achleitner, Martin, Steenblock, Charlotte, Dänhardt, Juliane et al.·Molecular psychiatry·2023

Researchers tested a treatment called therapeutic apheresis (a blood-cleaning procedure) in Long-COVID patients and found that those who improved had significant reductions in harmful immune molecules, fatty substances, and inflammatory markers in their blood. The study also showed that a blood protein called fibrinogen dropped by 70% after treatment, and abnormal blood clumping patterns disappeared. This suggests the treatment may work by removing specific harmful substances from the blood.

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[Myalgic Encephalitis/Chronic Fatigue Syndrome: Diagnostic and Therapeutic Approach and Biological Research].

Sato, Wakiro·Brain and nerve = Shinkei kenkyu no shinpo·2023

This article reviews what we currently know about ME/CFS, a serious illness marked by extreme tiredness, sleep problems, difficulty thinking clearly, and difficulty standing up without symptoms getting worse. A key feature is post-exertional malaise—when patients feel much worse after physical or mental activity—which means people with ME/CFS need to carefully manage their activity levels. The article summarizes current approaches to diagnosis and treatment, as well as recent scientific discoveries about what happens in the body during this disease.

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Stress-Induced Transcriptomic Changes in Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Reveal Disrupted Immune Signatures.

Van Booven, Derek J, Gamer, Jackson, Joseph, Andrew et al.·International journal of molecular sciences·2023

This study looked at how the bodies of women with ME/CFS respond to exercise compared to healthy women. Researchers collected blood samples at three points: before exercise, during maximum effort, and during recovery. While healthy women's immune cells showed normal changes during exercise, women with ME/CFS showed unusual immune system activity specifically during the recovery period—the time when post-exertional malaise (worsening of symptoms) typically occurs.

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[Post-COVID syndrome with fatigue and exercise intolerance: myalgic encephalomyelitis/chronic fatigue syndrome].

Renz-Polster, Herbert, Scheibenbogen, Carmen·Innere Medizin (Heidelberg, Germany)·2022

This article explains that ME/CFS is a serious neurological and immune system disease, often triggered by infections like COVID-19, characterized by extreme fatigue lasting at least 6 months and a unique symptom called post-exertional malaise (PEM)—where even mild activity causes symptoms to worsen hours or days later. The authors stress that ME/CFS is a distinct medical condition that should not be confused with ordinary tiredness, and while there is no cure yet, treatment focuses on managing symptoms, addressing related circulation problems, and helping patients conserve energy through pacing.

The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Dehhaghi, Mona, Panahi, Hamed Kazemi Shariat, Kavyani, Bahar et al.·Aging and disease·2022

This review examines how tryptophan, an amino acid we get from food, is processed differently in people with ME/CFS. The body normally converts tryptophan into important substances like serotonin (which affects mood) and NAD+, an energy molecule. The authors propose that this conversion process may become overactive in ME/CFS, depleting NAD+ and making fatigue worse. They suggest that NAD+ supplements might help reduce fatigue and improve quality of life.

[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.