COVID-19 and the central nervous system: What is the interplay?

Abstract

Since the outbreak of COVID-19 in 2019-2020, the highly contiguous disease caused by coronavirus 2 (SARS-CoV-2) spread worldwide in a short life span causing a disastrous effect and nearly 5.8 million deaths until February 2022. This global health crisis caused concerns about the disease's aetiology, epidemiology, and management. Understanding the virus's long- and short-term consequences on diverse human body organs and systems was one of the scientist's concerns despite the virus' respiratory system principal effect. Thus, after reporting neurological symptoms in approximately one-third of hospitalised patients with COVID-19, demonstrating how COVID-19 infects the central nervous system (CNS), causing neurodegenerative diseases in various patients and how the virus affects CNS function became quintessential. There are various mechanisms for COVID-19 pathophysiology, some implicating the potential virus invasion of the blood-brain barrier (BBB). Trans-synaptic and hematogenous routes are the main routes for the virus to pass through the barrier. Binding to the BBB endothelial cells is causing significant alterations in the permeability and integrity properties of the barrier, which cause an elevation of the incidence rate of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis among COVI-19 patients. COVID-19 patients developed neurological manifestations ranging from mild symptoms to severe diseases such as headache and loss of smell, encephalitis and CNS-mediated respiratory distress. However, encephalitis is not a common complication, and it has a significant mortality rate in severely ill patients due to the hyperactivation of the host immune response. Although more investigations are needed, severe COVID- 19 patients are considered at a high risk of neurodegenerative disorder as a long-term consequence of SARS-CoV-2 infection.