4.5 Article

COVID-19 and chronic fatigue syndrome: Is the worst yet to come?

Journal

MEDICAL HYPOTHESES
Volume 146, Issue -, Pages -

Publisher

CHURCHILL LIVINGSTONE
DOI: 10.1016/j.mehy.2020.110469

Keywords

Chronic fatigue syndrome; COVID-19; Glymphatic system; Idiopathic intracranial hypertension; Lymphatic system; Post-COVID-19 fatigue syndrome

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The concern of long-term sequelae resembling myalgic encephalomyelitis/chronic fatigue syndrome in COVID-19 patients has led to the need for clarifying mechanisms underlying post-COVID-19 fatigue syndrome. Integrating insights from various conditions, the study suggests a hypothesis involving damage to olfactory sensory neurons leading to congestion in the glymphatic system as a potential cause. Research is needed to confirm this hypothesis and explore the role of the glymphatic-lymphatic system in combating post-COVID-19 fatigue syndrome.
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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