Introduction
The novel severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2, causing COVID-19 infection, gave the world an unprecedented health blow, and in this regard, a lot of scientific inquiries on the biology of the disease were undertaken. In fact, though most of the focus has been upon respiratory issues, considerable neurological involvement is well supported by increasingly growing data. Neurotropism and the capability of SARS-CoV-2 to enter the CNS have raised an alert for its potential long-term neurological consequence. This article reviews the current understanding of neuropathogenesis caused by the novel coronavirus SARS-CoV-2, with a special focus on neurological symptoms, mechanisms of neuroinvasion, and potential long-term consequences.
Mechanisms of neuroinvasion
Its entry to the brain is thought to be via several routes. One hypothesis is that the virus enters the brain through the olfactory nerve, bypassing the blood-brain barrier. A high number of anosmias or loss of smell in COVID-19 patients supports this theory. Another possible route of dissemination is hematogenous: through infection of the virus in the blood-brain barrier endothelial cells, leading to increased permeability and allowing access of the virus into the central nervous system. The virus may also use the vagus nerve or other peripheral nerves to enter the brainstem and other parts of the central nervous system.
Once inside, these infections spread by hijacking the transport system, moving along axons inside neurons. Several infections also carry out cell-to-cell spread that avoids immune surveillance and extracellular space. Elucidation of these routes is essential in developing therapeutic strategies to prevent or reduce the outcomes of neuroinvasive diseases.
Because these ACE2 receptors are expressed in a general manner by several parts of the brain, including both neurons and glial cells, their neuropathogenesis might depend on the capability of SARS-CoV-2 to bind with these ACE2 receptors. One of the most likely mechanisms for neurotoxicity is a direct viral attack mediated by the spike viral protein through the ACE2 receptors. Moreover, severe manifestations of COVID-19 feature a hyperinflammatory status, also known as a “cytokine storm,” which leads to further CNS involvement because of an increase in the pervasive inflammation and oxidative stress, causing a further lesion of neural structures. Such knowledge is essential to treat neurological symptoms in COVID-19 patients and gives a chance for targeted therapy that may protect the nervous system from the long-term consequences of SARS-CoV-2 infection.
Neurological manifestations
Neurological manifestations of COVID-19 range from minor symptoms such as headache and dizziness to severe diseases such as encephalitis, stroke, and Guillain-Barre syndrome. Symptoms could be divided into three major categories: musculoskeletal issues, peripheral nervous system manifestations, and central nervous system complications.