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 HillebrandsSergio 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 journalArticleAcademicpeer-review

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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 languageEnglish
Pages (from-to)217-231.e8
Number of pages24
JournalCell stem cell
Issue number2
Early online date25-Dec-2021
Publication statusPublished - Feb-2022

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