SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

COVID Moonshot consortium; Jitske Jansen; Katharina C Reimer; James S Nagai; Finny S Varghese; Gijs J Overheul; Marit de Beer; Rona Roverts; Deniz Daviran; Liline A S Fermin; Brigith Willemsen; Marcel Beukenboom; Sonja Djudjaj; Saskia von Stillfried; Larissa E van Eijk; Mirjam Mastik; Marian Bulthuis; Wilfred den Dunnen; Harry van Goor; Jan-Luuk Hillebrands; Sergio H Triana; Theodore Alexandrov; Marie-Cherelle Timm; Bartholomeus T van den Berge; Martijn van den Broek; Quincy Nlandu; Joelle Heijnert; Eric M J Bindels; Remco M Hoogenboezem; Fieke Mooren; Christoph Kuppe; Pascal Miesen; Katrien Grünberg; Ties Ijzermans; Eric J Steenbergen; Jan Czogalla; Michiel F Schreuder; Nico Sommerdijk; Anat Akiva; Peter Boor; Victor G Puelles; Jürgen Floege; Tobias B Huber; Ronald P van Rij; Ivan G Costa; Rebekka K Schneider; Bart Smeets; Rafael Kramann

doi:10.1016/j.stem.2021.12.010

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

COVID Moonshot consortium
, Jitske Jansen
, Katharina C Reimer
, James S Nagai
, Finny S Varghese
, Gijs J Overheul
, Marit de Beer
, Rona Roverts
, Deniz Daviran
, Liline A S Fermin
, Brigith Willemsen
, Marcel Beukenboom
, Sonja Djudjaj
, Saskia von Stillfried
, Larissa E van Eijk
, Mirjam Mastik
, Marian Bulthuis
, Wilfred den Dunnen
, Harry van Goor
, Jan-Luuk Hillebrands

Sergio H Triana, Theodore Alexandrov, Marie-Cherelle Timm, Bartholomeus T van den Berge, Martijn van den Broek, Quincy Nlandu, Joelle Heijnert, Eric M J Bindels, Remco M Hoogenboezem, Fieke Mooren, Christoph Kuppe, Pascal Miesen, Katrien Grünberg, Ties Ijzermans, Eric J Steenbergen, Jan Czogalla, Michiel F Schreuder, Nico Sommerdijk, Anat Akiva, Peter Boor, Victor G Puelles, Jürgen Floege, Tobias B Huber, Ronald P van Rij, Ivan G Costa, Rebekka K Schneider, Bart Smeets, Rafael Kramann^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.

Original language	English
Pages (from-to)	217-231.e8
Number of pages	24
Journal	Cell stem cell
Volume	29
Issue number	2
Early online date	25-Dec-2021
DOIs	https://doi.org/10.1016/j.stem.2021.12.010
Publication status	Published - Feb-2022

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COVID Moonshot consortium, Jansen, J., Reimer, K. C., Nagai, J. S., Varghese, F. S., Overheul, G. J., de Beer, M., Roverts, R., Daviran, D., Fermin, L. A. S., Willemsen, B., Beukenboom, M., Djudjaj, S., von Stillfried, S., van Eijk, L. E., Mastik, M., Bulthuis, M., Dunnen, W. D., van Goor, H., ... Kramann, R. (2022). SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. Cell stem cell, 29(2), 217-231.e8. https://doi.org/10.1016/j.stem.2021.12.010

@article{235be09100ea434aa19bd133616cf16a,

title = "SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids",

abstract = "Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.",

author = "\{COVID Moonshot consortium\} and Jitske Jansen and Reimer, \{Katharina C\} and Nagai, \{James S\} and Varghese, \{Finny S\} and Overheul, \{Gijs J\} and \{de Beer\}, Marit and Rona Roverts and Deniz Daviran and Fermin, \{Liline A S\} and Brigith Willemsen and Marcel Beukenboom and Sonja Djudjaj and \{von Stillfried\}, Saskia and \{van Eijk\}, \{Larissa E\} and Mirjam Mastik and Marian Bulthuis and Dunnen, \{Wilfred den\} and \{van Goor\}, Harry and Jan-Luuk Hillebrands and Triana, \{Sergio H\} and Theodore Alexandrov and Marie-Cherelle Timm and \{van den Berge\}, \{Bartholomeus T\} and \{van den Broek\}, Martijn and Quincy Nlandu and Joelle Heijnert and Bindels, \{Eric M J\} and Hoogenboezem, \{Remco M\} and Fieke Mooren and Christoph Kuppe and Pascal Miesen and Katrien Gr{\"u}nberg and Ties Ijzermans and Steenbergen, \{Eric J\} and Jan Czogalla and Schreuder, \{Michiel F\} and Nico Sommerdijk and Anat Akiva and Peter Boor and Puelles, \{Victor G\} and J{\"u}rgen Floege and Huber, \{Tobias B\} and \{van Rij\}, \{Ronald P\} and Costa, \{Ivan G\} and Schneider, \{Rebekka K\} and Bart Smeets and Rafael Kramann",

year = "2022",

month = feb,

doi = "10.1016/j.stem.2021.12.010",

language = "English",

volume = "29",

pages = "217--231.e8",

journal = "Cell stem cell",

issn = "1934-5909",

publisher = "Cell Press",

number = "2",

}

COVID Moonshot consortium, Jansen, J, Reimer, KC, Nagai, JS, Varghese, FS, Overheul, GJ, de Beer, M, Roverts, R, Daviran, D, Fermin, LAS, Willemsen, B, Beukenboom, M, Djudjaj, S, von Stillfried, S, van Eijk, LE, Mastik, M, Bulthuis, M , Dunnen, WD , van Goor, H , Hillebrands, J-L, Triana, SH, Alexandrov, T, Timm, M-C, van den Berge, BT, van den Broek, M, Nlandu, Q, Heijnert, J, Bindels, EMJ, Hoogenboezem, RM, Mooren, F, Kuppe, C, Miesen, P, Grünberg, K, Ijzermans, T, Steenbergen, EJ, Czogalla, J, Schreuder, MF, Sommerdijk, N, Akiva, A, Boor, P, Puelles, VG, Floege, J, Huber, TB, van Rij, RP, Costa, IG, Schneider, RK, Smeets, B & Kramann, R 2022, 'SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids', Cell stem cell, vol. 29, no. 2, pp. 217-231.e8. https://doi.org/10.1016/j.stem.2021.12.010

TY - JOUR

T1 - SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

AU - COVID Moonshot consortium

AU - Jansen, Jitske

AU - Reimer, Katharina C

AU - Nagai, James S

AU - Varghese, Finny S

AU - Overheul, Gijs J

AU - de Beer, Marit

AU - Roverts, Rona

AU - Daviran, Deniz

AU - Fermin, Liline A S

AU - Willemsen, Brigith

AU - Beukenboom, Marcel

AU - Djudjaj, Sonja

AU - von Stillfried, Saskia

AU - van Eijk, Larissa E

AU - Mastik, Mirjam

AU - Bulthuis, Marian

AU - Dunnen, Wilfred den

AU - van Goor, Harry

AU - Hillebrands, Jan-Luuk

AU - Triana, Sergio H

AU - Alexandrov, Theodore

AU - Timm, Marie-Cherelle

AU - van den Berge, Bartholomeus T

AU - van den Broek, Martijn

AU - Nlandu, Quincy

AU - Heijnert, Joelle

AU - Bindels, Eric M J

AU - Hoogenboezem, Remco M

AU - Mooren, Fieke

AU - Kuppe, Christoph

AU - Miesen, Pascal

AU - Grünberg, Katrien

AU - Ijzermans, Ties

AU - Steenbergen, Eric J

AU - Czogalla, Jan

AU - Schreuder, Michiel F

AU - Sommerdijk, Nico

AU - Akiva, Anat

AU - Boor, Peter

AU - Puelles, Victor G

AU - Floege, Jürgen

AU - Huber, Tobias B

AU - van Rij, Ronald P

AU - Costa, Ivan G

AU - Schneider, Rebekka K

AU - Smeets, Bart

AU - Kramann, Rafael

PY - 2022/2

Y1 - 2022/2

N2 - Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.

AB - Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.

U2 - 10.1016/j.stem.2021.12.010

DO - 10.1016/j.stem.2021.12.010

M3 - Article

C2 - 35032430

SN - 1934-5909

VL - 29

SP - 217-231.e8

JO - Cell stem cell

JF - Cell stem cell

IS - 2

ER -

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

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