COVID-19-Associated Neurological Disorders: The Potential Route of CNS Invasion and Blood-Brain Barrier Relevance

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that has sparked a global pandemic of the coronavirus disease of 2019 (COVID-19). The virus invades human cells through the angiotensin-converting enzyme 2 (ACE2) receptor-driven pathway, primarily targeting the human respiratory tract. However, emerging reports of neurological manifestations demonstrate the neuroinvasive potential of SARS-CoV-2. This review highlights the possible routes by which SARS-CoV-2 may invade the central nervous system (CNS) and provides insight into recent case reports of COVID-19-associated neurological disorders, namely ischaemic stroke, encephalitis, encephalopathy, epilepsy, neurodegenerative diseases, and inflammatory-mediated neurological disorders. We hypothesize that SARS-CoV-2 neuroinvasion, neuroinflammation, and blood-brain barrier (BBB) dysfunction may be implicated in the development of the observed disorders; however, further research is critical to understand the detailed mechanisms and pathway of infectivity behind CNS pathogenesis.

Neuropsychiatric Complications of COVID-19

“…It is a human coronavirus (HCoV) in the beta genera of the coronaviridae family, along with severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), Middle East respiratory syndrome related coronavirus (MERS-CoV), HCoV-OC43, and HCoV-KHU1 [ 10 ]. During cell entry, SARS-CoV-2 binds angiotensin converting-enzyme 2 (ACE2) on the target cell surface to facilitate fusion of viral and host membranes [ 11 , 12 ]. ACE2 exists on cellular membranes in the lungs, gastrointestinal (GI) track, myocardium, renal tubules, and bladder [ 12 ].…”

Emerging Neurological and Psychobiological Aspects of COVID-19 Infection

“…On the other hand, Moriguchi et al [ 48 ] observed viral RNA in the cerebrospinal fluid of a patient with aseptic encephalitis and Paniz-Mandolfi et al [ 49 ] reported the presence of SARS-CoV-2 viral particles in the neuronal and capillary endothelial cells in the frontal lobe tissue in a postmortem study. It has therefore been suggested that SARS-CoV-2 neuroinvasion, neuroinflammation and impairment of the blood–brain barrier (BBB) are responsible for the neurological symptoms [ 50 ].…”

Rejuveinix Mitigates Sepsis-Associated Oxidative Stress in the Brain of Mice: Clinical Impact Potential in COVID-19 and Nervous System Disorders

“…More than a third of patients with COVID-19, especially those with severe to critical COVID-19 who managed on an intensive care unit (ICU) develop central nervous system (CNS) symptoms and signs (e.g., headache, dizziness, ataxia, seizure, delirium, confusion, impaired consciousness) consistent with CNS involvement and /or neurological complications (6)(7)(8)(9)(10)(11)(12)(13).…”

“…Cerebrovascular complications of viral sepsis, including ischemic or hemorrhagic stroke, CNS involvement in CRS, hypoxia as well as the interplay of comorbidities have been implicated as contributing factors (6)(7)(8)(9)(10)(11)(12)(13). Due to the neuro-invasive capability of SARS-CoV-2, acute disseminated encephalomyelitis (ADEM) and viral encephalitis have also been suspected in some patients (13).…”