biostudies-literatureKrasemann SBundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftFraunhofer-GesellschaftBMBF Berlinicare307-320https://www.ebi.ac.uk/biostudies/studies/S-EPMC8772030biostudies-literatureUnknown17(2)Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients' brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, we found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the Stem cell reportsThe blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2.PMC8772030840260FR1720/18-101EK1608B602015GL589/10-101EK1608A01KX2021Cubukova AZaliani AFranzenburg SLiang YMoese SMatschke JFranke AClaussen CZhang LLittau JLTon KSepulveda-Falla DGribbon PGerhartl AThies EGlatzel MRicklefs FPless OBodem JFriese MABrachner AHaferkamp UMuller FJHartmann KNeuhaus WKannt AGeisslinger GGeiger NPfefferle SFitzek AWoo MSHeinrich FAppelt-Menzel AKonig EMLeu JKrasemann SBarenberg JSperhake JOndruschka BSauvigny TSchweizer MfalseThe blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2.Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients' brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, we found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the 2022-01-01T00:00:00Z2022 Feb2026-05-09T20:36:16.88Z2022-02-11T16:02:44.029ZS-EPMC87720303506312510.1016/j.stemcr.2021.12.011