LAUSR

Early reports from Wuhan suggested that 36% of COVID-19 patients show neurological symptoms, later European studies showed as much as 60%;cases of viral encephalitis have been reported. This suggests that the virus might be neurotropic under unknown circumstances. This is well established for other coronaviruses. Many questions remain with regard to the current pandemic, including the influence of SARS-COV-2 on the developing brain. In order to understand why some patients develop such symptoms and others do not and whether developing brain might be more susceptible than adult counterpart, we addressed the infectability of the central nervous system (CNS). Reports that the ACE2 receptor - critical for virus entry into lung cells - is found in different neurons support this expectation. We employed a human induced pluripotent stem cell (iPSC)-derived BrainSphere model. A short-term infection of the BrainSpheres with SARS-CoV-2 led to infection of a fraction of neural cells with replication of the virus evident at 72 hpi. Virus particles were found in the neuronal cell bodies extending into apparent neurite structures. PCR measurements corroborated the replication of the virus, suggesting at least a tenfold increase in virus copies per total RNA. Immature and more mature cultures have been compared. 12week BrainSpheres were more sensitive to infection than 5-week ones, suggesting that maturation processes (such as synaptogenesis and network formation) might render more sensitive to the infection. These findings were supported by others in similar brain organoid models. These recent findings will be summarized to understand the advantages and limitations of brain organoids in infectious diseases in particular for the developing nervous system, as brain organoids mimic embryonic stages of development.