**4.3 Proposed mechanisms of coronavirus entry into the nervous system**


circumventricular organs are particularly vulnerable to circulating inflammatory mediators.


Spike (S) proteins bind the angiotensin-converting enzyme 2 (ACE-2) receptor of the target cell. Cleavage of the S protein by type II transmembrane serine protease (TMPRSS2), facilitates viral entry. ACE-2 mRNA expression and double-positive ACE-2 + TMPRSS2 + cells have been identified, among others, on neurons and glial

#### **Figure 4.**

*Scheme illustration of the neurotropism, neuroinflammatory processes, and effects on brain cells triggered by COVID-19 in patients. Image and description text adapted from [59].*

#### *Neurological Effects of COVID-19 and Its Treatment/Management DOI: http://dx.doi.org/10.5772/intechopen.105730*

cells, in the cerebral cortex, striatum, hypothalamus, substantia nigra, and brain stem, making the CNS potential direct targets of SARS-CoV-2 infection.

Immune cells from the periphery and the central nervous system (CNS) (A) Produce effector molecules that include pro-inflammatory cytokines and autoantibodies. (B) SARS-CoV-2 infection also causes leakage of the blood–brain barrier leading in some cases to hemorrhage and cerebral infarct, as well as eliciting leukocyte infiltration. (C) In the parenchyma, the CNS cells become infected by SARS-CoV via angiotensin-converting enzyme 2 (ACE2) endocytosis mediated by the two-pore channel 2 (TCP2). (D) SARS-CoV-2 infection leads to loss of physiological functions of the brain cells, including neurons, astrocytes, microglia, and oligodendrocytes. Cell types are identified in the following manner; A, Astrocyte; L, Leukocyte; M, Microglia; N, Neurone; O, Oligodendrocyte.
