Abstract
Widespread damage to the central and peripheral nervous systems resulting from COVID-19 is becoming well established. Features include impairments of the level [somnolence, stupor, coma] and content [confusion, delirium] of consciousness, impaired senses of taste, smell and vision as well as skeletal muscle manifestations. The neuroinvasive nature of SARS-CoV-2 may contribute to the acute respiratory failure of COVID-19. SARS-CoV-1 virus was detected in the brain of infected patients along with neuronal necrosis and glial hyperplasia. In SARS-CoV-2, modifications of crucial cellular pathways [mitochondrial function, proteolysis, lipid metabolism] known to be implicated in cellular aging and in neurodegenerative diseases occur. Adamantanes, [amantadine and the structurally-related memantine] are employed for the treatment of disorders of consciousness while also manifesting effective antiviral properties. Clinical studies and Case Reports at this early stage of COVID-19 reveal evidence of a protective effect of amantadine in infected patients with benefit being ascribed to amantadine’s effects on viral release into the host cell via mechanisms involving the E channel of the virus or by the agent’s down-regulation of the host protease Cathepsin L in addition to disruption of the lysosomal pathway. Memantine has potent neuroprotective actions in both wellestablished neurodegenerative diseases as well as in viral disorders in which it prevents neuronal cell loss and concomitantly reduces viral replication in a dose-dependent manner. Controlled clinical trials for the assessment of efficacy of these adamantanes for the prevention and treatment of COVID-19 are now indicated.
Highlights
Reports of the involvement of the CNS in relation to COVID-19 continue to appear
The neuroinvasive properties of SARSCoV-2 may contribute to the acute respiratory failure characteristic of COVID-19 and modifications of mitochondrial function, proteolysis and lipid metabolism characteristic of neurodegenerative diseases have been shown to occur
Basic research in molecular virology has identified mechanisms whereby members of the adamantine family of agents such as amantadine and memantine have significant antiviral properties with the capacity to impair replication of the virus. Their well-established neurobiological mechanisms such as NMDA receptor antagonist actions are effective for the treatment of motor dysfunction and disorders of consciousness associated with a range of conditions including PD, traumatic brain injury as well as in human coronaviral infections
Summary
Reports of the involvement of the CNS in relation to COVID-19 continue to appear. In a review of 214 hospitalized patients from Wuhan, China RT-PCR -confirmed diagnosis of COVID-19, neurological symptoms occurred in 45.5% of those with severe infection. Mechanisms involved in the pathogenesis of the CNS manifestations of COVID-19 have not been definitively established but the presence of pro-inflammatory biomarkers in these patients suggests that SARS-CoV-2 related inflammatory mechanisms such as a “cytokine storm” could be implicated [6]. Amantadine and its structurally-related derivative memantine are members of the adamantane family that are commonly-prescribed for the treatment of CNS disorders (Table 2).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
