02261nas a2200445   4500000000100000000000100001008004100002260001500043653003600058653001200094653002400106653001300130653002500143653001900168653001700187653001100204653002300215653001400238653001500252653001500267653001800282653002600300653001900326653002200345653002300367653002900390100002100419700001700440700002100457700001900478700001500497700002100512700001700533700002600550245010800576300001500684490000700699520109500706022001401801       2020                            d  c2020-12-0310aAngiotensin-Converting Enzyme 210aAnimals10aBlood-Brain Barrier10aCOVID-1910aChlorocebus aethiops10aChoroid Plexus10aHEK293 Cells10aHumans10aModels, Biological10aorganoids10aSARS-CoV-210aVero Cells10aViral Tropism10aVirus Internalization10aapolipoprotein10ablood-CSF-barrier10acerebral organoids10achoroid plexus organoids1 aLaura Pellegrini1 aAnna Albecka1 aDonna L. Mallery1 aMax J. Kellner1 aDavid Paul1 aAndrew P. Carter1 aLeo C. James1 aMadeline A. Lancaster00aSARS-CoV-2 Infects the Brain Choroid Plexus and Disrupts the Blood-CSF Barrier in Human Brain Organoids  a951-961.e50 v273 aCoronavirus 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.  a1875-9777