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. 2020 Nov 16;11:583459. doi: 10.3389/fneur.2020.583459

Figure 1.

Figure 1

The potential routes of SARS-CoV-2 neurological invasion. (1) SARS-CoV-2-containing droplets are deposited on the mucosa membranes through intranasal delivery, (2) Accordingly, the virus can infect the peripheral nervous system using the neuronal retrograde route until it reaches the brain. (3) SARS-CoV-2 binds to ACE2 receptors expressed on epithelial cells and enters the respiratory tract, (4) Alternatively, SARS-CoV-2 can enter the bloodstream by the hematogenous route and (5) transmigrate the BBB through receptor (ACE2) binding transcytosis/endocytosis on the endothelial monolayers. Once SARS-CoV-2 reaches the brain, it can infect the brain cells, probably the astrocytes and microglia or can infect the neurons directly. SARS-CoV-2 can infect and activate both astrocytes and microglia causing a release virion, viral proteins, host-inflammatory molecules and other neurotoxins that cause neuronal damage and disease. Furthermore, infection with SARS-CoV-2 can indirectly trigger neurological injury through an exaggerated immune response and by the hypoxic environment caused by respiratory distress.