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The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2

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The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2. / Krasemann, Susanne; Haferkamp, Undine; Pfefferle, Susanne; Woo, Marcel S; Heinrich, Fabian; Schweizer, Michaela; Appelt-Menzel, Antje; Cubukova, Alevtina; Barenberg, Janica; Leu, Jennifer; Hartmann, Kristin; Thies, Edda; Littau, Jessica Lisa; Sepulveda-Falla, Diego; Zhang, Liang; Ton, Kathy; Liang, Yan; Matschke, Jakob; Ricklefs, Franz; Sauvigny, Thomas; Sperhake, Jan; Fitzek, Antonia; Gerhartl, Anna; Brachner, Andreas; Geiger, Nina; König, Eva-Maria; Bodem, Jochen; Franzenburg, Sören; Franke, Andre; Moese, Stefan; Müller, Franz-Josef; Geisslinger, Gerd; Claussen, Carsten; Kannt, Aimo; Zaliani, Andrea; Gribbon, Philip; Ondruschka, Benjamin; Neuhaus, Winfried; Friese, Manuel A; Glatzel, Markus; Pless, Ole.

In: STEM CELL REP, Vol. 17, No. 2, 08.02.2022, p. 307-320.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Krasemann, S, Haferkamp, U, Pfefferle, S, Woo, MS, Heinrich, F, Schweizer, M, Appelt-Menzel, A, Cubukova, A, Barenberg, J, Leu, J, Hartmann, K, Thies, E, Littau, JL, Sepulveda-Falla, D, Zhang, L, Ton, K, Liang, Y, Matschke, J, Ricklefs, F, Sauvigny, T, Sperhake, J, Fitzek, A, Gerhartl, A, Brachner, A, Geiger, N, König, E-M, Bodem, J, Franzenburg, S, Franke, A, Moese, S, Müller, F-J, Geisslinger, G, Claussen, C, Kannt, A, Zaliani, A, Gribbon, P, Ondruschka, B, Neuhaus, W, Friese, MA, Glatzel, M & Pless, O 2022, 'The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2', STEM CELL REP, vol. 17, no. 2, pp. 307-320. https://doi.org/10.1016/j.stemcr.2021.12.011

APA

Krasemann, S., Haferkamp, U., Pfefferle, S., Woo, M. S., Heinrich, F., Schweizer, M., Appelt-Menzel, A., Cubukova, A., Barenberg, J., Leu, J., Hartmann, K., Thies, E., Littau, J. L., Sepulveda-Falla, D., Zhang, L., Ton, K., Liang, Y., Matschke, J., Ricklefs, F., ... Pless, O. (2022). The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2. STEM CELL REP, 17(2), 307-320. https://doi.org/10.1016/j.stemcr.2021.12.011

Vancouver

Krasemann S, Haferkamp U, Pfefferle S, Woo MS, Heinrich F, Schweizer M et al. The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2. STEM CELL REP. 2022 Feb 8;17(2):307-320. https://doi.org/10.1016/j.stemcr.2021.12.011

Bibtex

@article{bfd7e6b1adc347608d557a82585f3d15,
title = "The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2",
abstract = "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 blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.",
author = "Susanne Krasemann and Undine Haferkamp and Susanne Pfefferle and Woo, {Marcel S} and Fabian Heinrich and Michaela Schweizer and Antje Appelt-Menzel and Alevtina Cubukova and Janica Barenberg and Jennifer Leu and Kristin Hartmann and Edda Thies and Littau, {Jessica Lisa} and Diego Sepulveda-Falla and Liang Zhang and Kathy Ton and Yan Liang and Jakob Matschke and Franz Ricklefs and Thomas Sauvigny and Jan Sperhake and Antonia Fitzek and Anna Gerhartl and Andreas Brachner and Nina Geiger and Eva-Maria K{\"o}nig and Jochen Bodem and S{\"o}ren Franzenburg and Andre Franke and Stefan Moese and Franz-Josef M{\"u}ller and Gerd Geisslinger and Carsten Claussen and Aimo Kannt and Andrea Zaliani and Philip Gribbon and Benjamin Ondruschka and Winfried Neuhaus and Friese, {Manuel A} and Markus Glatzel and Ole Pless",
note = "Copyright {\textcopyright} 2021 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2022",
month = feb,
day = "8",
doi = "10.1016/j.stemcr.2021.12.011",
language = "English",
volume = "17",
pages = "307--320",
journal = "STEM CELL REP",
issn = "2213-6711",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2

AU - Krasemann, Susanne

AU - Haferkamp, Undine

AU - Pfefferle, Susanne

AU - Woo, Marcel S

AU - Heinrich, Fabian

AU - Schweizer, Michaela

AU - Appelt-Menzel, Antje

AU - Cubukova, Alevtina

AU - Barenberg, Janica

AU - Leu, Jennifer

AU - Hartmann, Kristin

AU - Thies, Edda

AU - Littau, Jessica Lisa

AU - Sepulveda-Falla, Diego

AU - Zhang, Liang

AU - Ton, Kathy

AU - Liang, Yan

AU - Matschke, Jakob

AU - Ricklefs, Franz

AU - Sauvigny, Thomas

AU - Sperhake, Jan

AU - Fitzek, Antonia

AU - Gerhartl, Anna

AU - Brachner, Andreas

AU - Geiger, Nina

AU - König, Eva-Maria

AU - Bodem, Jochen

AU - Franzenburg, Sören

AU - Franke, Andre

AU - Moese, Stefan

AU - Müller, Franz-Josef

AU - Geisslinger, Gerd

AU - Claussen, Carsten

AU - Kannt, Aimo

AU - Zaliani, Andrea

AU - Gribbon, Philip

AU - Ondruschka, Benjamin

AU - Neuhaus, Winfried

AU - Friese, Manuel A

AU - Glatzel, Markus

AU - Pless, Ole

N1 - Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2022/2/8

Y1 - 2022/2/8

N2 - 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 blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.

AB - 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 blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.

U2 - 10.1016/j.stemcr.2021.12.011

DO - 10.1016/j.stemcr.2021.12.011

M3 - SCORING: Journal article

C2 - 35063125

VL - 17

SP - 307

EP - 320

JO - STEM CELL REP

JF - STEM CELL REP

SN - 2213-6711

IS - 2

ER -