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 F. Mastik
- Marian Bulthuis
- Wilfred F.A. den Dunnen
- Harry van Goor
- Jan‐Luuk Hillebrands
- Sergio Triana
- Theodore Alexandrov
- M. Cherelle Timm
- Bartholomeus T. van den Berge
- Martijn van den Broek
- Quincy Nlandu
- Joelle Heijnert
- Eric M. Bindels
- Remco M. Hoogenboezem
- Fieke Mooren
- Christoph Kuppe
- Pascal Miesen
- Katrien Grünberg
- Ties Ijzermans
- Eric J. Steenbergen
- Jan Czogalla
- Michiel F. Schreuder
- Nico A. J. M. Sommerdijk
- Anat Akiva
- Peter Boor
- Victor G. Puelles
- Jürgen Floege
- Tobias B. Huber
- Hagit Achdout
- A. Aimon
- Elad Bar-David
- Haim Barr
- Amir Ben‐Shmuel
- James M. Bennett
- Melissa L. Boby
- Bruce Borden
- Gregory R. Bowman
- Juliane Brun
- Sarma BVNBS
- Mark Calmiano
- Anna Carbery
- Emma Cattermole
- Eugene Chernychenko
- John D. Choder
- Austin Clyde
- Joseph E. Coffland
- Galit Cohen
- Jason C. Cole
- Alessandro Contini
- Lisa Sanderson Cox
- Milan Cvitkovic
- Alex Dias
- Kim Donckers
- David Dotson
- Alica Douangamath
- Shirly Duberstein
- Tim Dudgeon
- Louise Dunnett
- Peter Eastman
- Noam Erez
- Charles J. Eyermann
- Mike Fairhead
- Gwen Fate
- D. Fearon
- Oleg Federov
- Matteo P. Ferla
- R.S. Fernandes
- Lori Ferrins
- Richard Foster
- Holly Foster
- Ronen Gabizon
- Adolfo García‐Sastre
- Victor O. Gawriljuk
- Paul Gehrtz
- C. Gileadi
- Charline Giroud
- William G. Glass
- Robert C. Glen
- Itai glinert
- André S. Godoy
- Marian V. Gorichko
- T.J. Gorrie-Stone
- Ed Griffen
- Storm Hassell Hart
- Jag Heer
- Micheal Henry
- FDF. von Delft
Cell stem cell · 2021 · Elsevier BV
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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.