In addition to the well-known respiratory symptoms, COVID-19 patients suffer from a loss of smell and taste, headache, impaired consciousness, and nerve pain. Raising possibility of virus infiltration in the nervous system, including brain. Despite cases emerging of COVID-19 patients with neurologic manifestations, potential neurotropic mechanisms underlying SARS-CoV-2-mediated entry into the cells of the brain are largely unexplored. Evidenced by transgenic mice models. The evolutionarily-related coronaviruses, such as SARS-CoV and MERS-CoV, can invade the brain by replicating and spreading through the nasal cavity, and possibly olfactory bulbs located in close proximity to the frontal lobes of the brain. Once inside the brain, viruses can harm the brain directly and indirectly by infecting the cells and myelin sheaths, and by activating microglia, which may in turn consume healthy neurons to induce neuroinflammation and neurodegeneration.