ReviewMedical hypotheses2021
COVID-19 and chronic fatigue syndrome: Is the worst yet to come?
Review in Medical hypotheses, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19.Brain, behavior, and immunity · 2022Pooled it
- More than 50 long-term effects of COVID-19: a systematic review and meta-analysis.Scientific reports · 2021Pooled it
- Follow-Ups on Persistent Symptoms and Pulmonary Function Among Post-Acute COVID-19 Patients: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2021Pooled it
- A randomized open-label clinical trial on the effect of Amantadine on post Covid 19 fatigue.Scientific reports · 2024Trial
- The Effect of Using a Rehabilitation Robot for Patients with Post-Coronavirus Disease (COVID-19) Fatigue Syndrome.Sensors (Basel, Switzerland) · 2023Trial
- Application of an EMG-Rehabilitation Robot in Patients with Post-Coronavirus Fatigue Syndrome (COVID-19)-A Feasibility Study.International journal of environmental research and public health · 2022Trial
- Testing the Feasibility of a Self-Help Intervention That Includes Lymphatic Drainage to Reduce Fatigue-Related Symptoms Among Patients with Long COVID in General Practice: Experiences from Our Randomized Controlled Trial (RCT).Infectious diseases and therapy · 2026Article
- Physical activity and sedentariness levels in patients with post-exertional malaise resulting from post-COVID-19 syndrome.Work (Reading, Mass.) · 2025Article
- Retracted: Chronic Epipharyngitis Treated with Epipharyngeal Abrasion Therapy: Symptoms, Diagnosis, Pathogenesis, and Treatment Outcomes.JMA journal · 2025Review
- Exploring Medium- and Long-Term Respiratory and Functional Sequelae in Young Adults Post-COVID-19.Medicina (Kaunas, Lithuania) · 2025Article
- A longitudinal study to COVID-19 infection among university students: Physical fitness changes and psychological responses.Journal of exercise science and fitness · 2025Article
- Medicinal plants for the management of post-COVID-19 fatigue: A literature review on the role and mechanisms.Journal of traditional and complementary medicine · 2025Review
- Dynamic brain glymphatic changes and cognitive function in COVID-19 recovered patients: a DTI-ALPS prospective cohort study.Frontiers in psychology · 2025Article
- Neuropsychiatric Manifestations of COVID-19 Disease and Post COVID Syndrome: The Role of N-acetylcysteine and Acetyl-L-carnitine.Current neuropharmacology · 2025Review
- A Comparative Study on the Pain Threshold Experienced by Fibromyalgia Patients Following Acute SARS-CoV-2 Infection.Life (Basel, Switzerland) · 2024Article
- Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Research progress of post-acute sequelae after SARS-CoV-2 infection.Cell death & disease · 2024Review
- Tackling Post-COVID-19 Rehabilitation Challenges: A Pilot Clinical Trial Investigating the Role of Robotic-Assisted Hand Rehabilitation.Journal of clinical medicine · 2024Article
- A perspective on the evidence for glymphatic obstruction in spaceflight associated neuro-ocular syndrome and fatigue.NPJ microgravity · 2024Review
- Glymphatic system dysfunction in recovered patients with mild COVID-19: A DTI-ALPS study.iScience · 2024Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There has been concern about possible long-term sequelae resembling myalgic encephalomyelitis/chronic fatigue syndrome in COVID-19 patients. Clarifying the mechanisms underlying such a "post-COVID-19 fatigue syndrome" is essential for the development of preventive and early treatment methods for this syndrome. In the present paper, by integrating insights pertaining to the glymphatic system and the nasal cerebrospinal fluid outflow pathway with findings in patients with chronic fatigue syndrome, idiopathic intracranial hypertension, and COVID-19, I provide a coherent conceptual framework for understanding the pathophysiology of post-COVID-19 fatigue syndrome. According to this hypothesis, this syndrome may result from damage to olfactory sensory neurons, causing reduced outflow of cerebrospinal fluid through the cribriform plate, and further leading to congestion of the glymphatic system with subsequent toxic build-up within the central nervous system. I further postulate that patients with post-COVID-19 fatigue syndrome may benefit from cerebrospinal fluid drainage by restoring glymphatic transport and waste removal from the brain. Obviously, further research is required to provide further evidence for the presence of this post-viral syndrome, and to provide additional insight regarding the relative contribution of the glymphatic-lymphatic system to it. Other mechanisms may also be involved. If confirmed, the glymphatic-lymphatic system could represent a target in combating post-COVID-19 fatigue syndrome. Moreover, further research in this area could also provide new insights into the understanding of chronic fatigue syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.