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

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; COVID Moonshot consortium

doi:10.1016/j.stem.2021.12.010

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

Standard

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. / Jansen, Jitske; Reimer, Katharina C; Nagai, James S; Varghese, Finny S; Overheul, Gijs J; de Beer, Marit; Roverts, Rona; Daviran, Deniz; Fermin, Liline A S; Willemsen, Brigith; Beukenboom, Marcel; Djudjaj, Sonja; von Stillfried, Saskia; van Eijk, Larissa E; Mastik, Mirjam; Bulthuis, Marian; Dunnen, Wilfred den; van Goor, Harry; Hillebrands, Jan-Luuk; Triana, Sergio H; Alexandrov, Theodore; Timm, Marie-Cherelle; van den Berge, Bartholomeus T; van den Broek, Martijn; Nlandu, Quincy; Heijnert, Joelle; Bindels, Eric M J; Hoogenboezem, Remco M; Mooren, Fieke; Kuppe, Christoph; Miesen, Pascal; Grünberg, Katrien; Ijzermans, Ties; Steenbergen, Eric J; Czogalla, Jan; Schreuder, Michiel F; Sommerdijk, Nico; Akiva, Anat; Boor, Peter; Puelles, Victor G; Floege, Jürgen; Huber, Tobias B; van Rij, Ronald P; Costa, Ivan G; Schneider, Rebekka K; Smeets, Bart; Kramann, Rafael; COVID Moonshot consortium.

In: CELL STEM CELL, Vol. 29, No. 2, 03.02.2022, p. 217-231.e8.

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

Harvard

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 & COVID Moonshot consortium 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

APA

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., Hillebrands, J-L., ... COVID Moonshot consortium (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

Vancouver

Jansen J, Reimer KC, Nagai JS, Varghese FS, Overheul GJ, de Beer M et al. SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. CELL STEM CELL. 2022 Feb 3;29(2):217-231.e8. https://doi.org/10.1016/j.stem.2021.12.010

Bibtex

@article{824fcc2ce9f64e1181d95d31ca314ffa,

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.",

keywords = "COVID-19/complications, Fibrosis, Humans, Kidney, Organoids/pathology, SARS-CoV-2",

author = "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 and {COVID Moonshot consortium}",

year = "2022",

month = feb,

day = "3",

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",

}

RIS

TY - JOUR

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

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

AU - COVID Moonshot consortium

PY - 2022/2/3

Y1 - 2022/2/3

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.

KW - COVID-19/complications

KW - Fibrosis

KW - Humans

KW - Kidney

KW - Organoids/pathology

KW - SARS-CoV-2

U2 - 10.1016/j.stem.2021.12.010

DO - 10.1016/j.stem.2021.12.010

M3 - SCORING: Journal article

C2 - 35032430

VL - 29

SP - 217-231.e8

JO - CELL STEM CELL

JF - CELL STEM CELL

SN - 1934-5909

IS - 2

ER -