Cases have emerged in which patients had clinical manifestations of encephalitis and positive results of SARS-CoV-2 in cerebrospinal fluid (CSF). However, these findings cannot prove the neurotropism of SARS-CoV-2 directly, since the CSF may also contain the virus from the meninges and cerebral microvasculatures. In fact, based on the HPA and Genotype Tissue Expression (GTEx) databases, the CNS cells express rather low levels of TMPRSS2, which are required by SARS-CoV-2 for host cell entry [12]. Lately, Bullen et al. reported the potential neurotropism of SARS-CoV-2 by employing a human induced pluripotent stem cell (iPSC)-derived BrainSphere mode [13]. Virus infection and replication can be observed in BrainSphere despite the TMPRSS2 gene expression being below the detection limit, suggesting alternative processing. In fact, a few proteins are found to act as co-factors for viral entry. A Disintegrin and Metalloproteases 17 (ADAM17) is a co-factor that can compete with TMPRSS2 or work independently for ACE2 shedding, and down regulation of ADAM17 by siRNA may result in a decreased in SARS-CoV infection [14]. According to HPA database, ADAM17 is more widely distributed than TMPRSS2 in human brain tissue [12]. Nevertheless, it should be emphasized that the current information is far from complete. Several aspects still remain to be elucidated before drawing a final conclusion about the neurotropism of SARS-CoV-2, such as the potential host receptors and infection co-factors, the susceptibility of CNS resident cells, as well as possible host–pathogen interactions on ACE2/TMPRSS2 expression.