Summary Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human-pluripotent-stem-cell-derived brain organoids to examine SARS-CoV-2 neurotropism. We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells but little to no infection of neurons or glia. We find that infected cells are apolipoprotein- and ACE2-expressing cells of the choroid plexus epithelial barrier. Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells, and cytokines into cerebrospinal fluid and the brain. Graphical Abstract Highlights • SARS-CoV-2 entry factors are expressed in choroid plexus (ChP) cells • More mature lipid-producing ChP cells could be more susceptible to SARS-CoV-2 infection • SARS-CoV-2 productively infects ChP, but not neurons, in organoids • SARS-CoV-2 infection damages the ChP epithelium, causing leakage of this brain barrier Increasing reports show neurological symptoms in COVID-19 patients, but it is still unclear whether SARS-CoV-2 can directly damage neurons. Lancaster and colleagues investigate viral neurotropism using brain organoids and discover that SARS-CoV-2 does not significantly infect neurons but productively infects choroid plexus, leading to damage of this brain barrier.
【저자키워드】 COVID-19, SARS-CoV-2, Apolipoprotein, Cerebral organoids, choroid plexus organoids, blood-CSF-barrier, 【초록키워드】 Coronavirus disease 2019, coronavirus, Lipoproteins, SARS-COV-2 infection, Infection, cytokine, virus, Brain, pseudovirus, Complication, immune cells, Pathogens, cerebrospinal fluid, expression, epithelial, patients, COVID-19 patients, Live virus, SARS-CoV-2 spike, SARS-CoV-2 neurotropism, neurons, Glia, SARS-CoV-2 entry factor, Organoid, epithelial cell, Neuron, cell types, viral tropism, acute respiratory syndrome, respiratory symptom, receptor ACE2, infected cell, infect, brain organoid, susceptible, Prevent, Cell, Neurological symptom, caused, significantly, expressed, expressing, Increasing, ACE2-expressing cell, infection with SARS-CoV-2, 【제목키워드】 Human, Organoid, barrier, choroid, Plexus,