Figure 1.

SARS-CoV-2 Potential Entry Routes to the CNS. SARS-CoV-2 may reach CNS using two main routes: the olfactory epithelium or the hematogenous (blood) routes. When entering through the olfactory epithelium, viral particles would have access to the CNS using transneuronal/synaptic pathways. Following neuronal infection, viral particles released may infect microglia and astrocytes. In the hematogenous entry route, endothelial cells may become infected, followed by perivascular astrocytes and perivascular macrophages. Secondarily, viral particles may reach microglia and neurons. Also during viremia in severe affected patients, SARS-CoV-2 can reach choroid plexus and circumventricular organs, which lack of BBB, and subsequently entering to brain parenchyma. A third possibility of CNS infection may arise after BBB breakdown as a consequence of systemic inflammation and cytokine release. Increased BBB permeability could facilitate SARS-CoV-2 entrance to the CNS.

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; CNS = central nervous system; CSF = cerebrospinal fluid; BBB = blood–brain barrier.