Neurological manifestations of SARS-CoV-2: complexity, mechanism and associated disorders

Abstract

Background

Coronaviruses such as Severe Acute Respiratory Syndrome coronavirus (SARS), Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are associated with critical illnesses, including severe respiratory disorders. SARS-CoV-2 is the causative agent of the deadly COVID-19 illness, which has spread globally as a pandemic. SARS-CoV-2 may enter the human body through olfactory lobes and interact with the angiotensin-converting enzyme2 (ACE2) receptor, further facilitating cell binding and entry into the cells. Reports have shown that the virus can pass through the blood–brain barrier (BBB) and enter the central nervous system (CNS), resulting in various disorders. Cell entry by SARS-CoV-2 largely relies on TMPRSS2 and cathepsin L, which activate S protein. TMPRSS2 is found on the cell surface of respiratory, gastrointestinal and urogenital epithelium, while cathepsin-L is a part of endosomes.

Aim

The current review aims to provide information on how SARS-CoV-2 infection affects brain function.. Furthermore, CNS disorders associated with SARS-CoV-2 infection, including ischemic stroke, cerebral venous thrombosis, Guillain–Barré syndrome, multiple sclerosis, meningitis, and encephalitis, are discussed. The many probable mechanisms and paths involved in developing cerebrovascular problems in COVID patients are thoroughly detailed.

Main body

There have been reports that the SARS-CoV-2 virus can cross the blood–brain barrier (BBB) and enter the central nervous system (CNS), where it could cause a various illnesses. Patients suffering from COVID-19 experience a range of neurological complications, including sleep disorders, viral encephalitis, headaches, dysgeusia, and cognitive impairment. The presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of COVID-19 patients has been reported. Health experts also reported its presence in cortical neurons and human brain organoids. The possible mechanism of virus infiltration into the brain can be neurotropic, direct infiltration and cytokine storm-based pathways. The olfactory lobes could also be the primary pathway for the entrance of SARS-CoV-2 into the brain.

Conclusions

SARS-CoV-2 can lead to neurological complications, such as cerebrovascular manifestations, motor movement complications, and cognitive decline. COVID-19 infection can result in cerebrovascular symptoms and diseases, such as strokes and thrombosis. The virus can affect the neural system, disrupt cognitive function and cause neurological disorders. To combat the epidemic, it is crucial to repurpose drugs currently in use quickly and develop novel therapeutics.

Highlights

• SARS-CoV-2, causative agent of COVID-19 which halted the world, has neurological implications.

• Viruses infiltrate the nervous system by vesicle-mediated transport, transcytosis, molecular envelope technology, neurotropism, and direct invasion.

• Olfactory invasion by SARS-CoV-2 and ACE2 expression in the brain lead to an increase in lung infection cases.

• Encephalitis, Multiple Sclerosis, Ischemic Stroke etc. are some of the diseases which are a result of neuroinvasion by SARS-CoV-2.