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

作者：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, Michelle L. Hill, Sam Horrell, Matthew F. D. Hurley, Tomer Israely, Andrew J. Jajack, Eric Jnoff, Dirk Jochmans, Tobias John, Steven De Jonghe, A.L. Kantsadi, Peter W. Kenny, J. L. Kiappes, L. Koekemoer, Boris Kovar, T. Krojer, Alpha A. Lee, Bruce A. Lefker, Haim Levy, Nir London, Petra Lukacik, Hannah Bruce Macdonald, Beth Maclean, Tika R. Malla, Tatiana Matviiuk, Willam McCorkindale, Briana L McGovern, Sharon Melamed, Oleg Michurin, Halina Mikolajek, Bruce F. Milne, Aaron Morris, Garret M. Morris, M. Jane Morwitzer, Demetri T. Moustakas, A.M. Nakamura, J. Brandão-Neto, Johan Neyts, Luong Viet Nguyen, G.D. Noske, Vladimiras Oleinikovas, Glaucius Oliva, Gijs J. Overheul, David Owen, Vladimír Pšenák, Ruby Pai, Jin Pan, Nir Paran, Benjamin Perry, Maneesh Pingle, Jakir Pinjari, Boaz Politi, A.J. Powell, Reut Puni, V.L. Rangel, Ranbabu N. Reddi, St Patrick Reid, Efrat Resnick, Emily Grace Ripka, Matthew C. Robinson, Ralph P. Robinson, Jaime Rodrı́guez-Guerra, Romel Rosales, Dominic A. Rufa, Chris Schofield, Mikhail Shafeev, Aarif L. Shaikh, Jiye Shi, Khriesto A. Shurrush, S.I. Bright Sing, Assa Sittner, R. Skyner, Adam P. Smalley, Mihaela Smilova, Leonardo J. Solmesky, John Spencer, Claire Strain-Damarell, Vishwanath Swamy, Hadas Tamir, Rachael E. Tennant, Warren Thompson, Andrew Thompson, Warren Thompson, Susana Tomasia, Anthony Tumber, Ioannis Vakonakis, Ronald P. van Rij, Laura van Geel, Finny S. Varghese, M. Vaschetto, Einat B. Vitner, Vincent A. Voelz, Andra Volkamer, F. von Delft, Annette von Delft, Martin Walsh, Walter H.J. Ward, Charlie Weatherall, Shay Weiss, Kris M. White, Conor Wild, Matthew Wittmann, Nathan D. Wright, Yfat Yahalom-Ronen, Daniel Zaidmann, Hadeer Zidane, Nicole Zitzmann, Ronald P. van Rij, Ivan G. Costa, Rebekka K. Schneider, Bart Smeets, Rafael Kramann · 发表于：Cell stem cell · 年份：2021 · DOI：10.1016/j.stem.2021.12.010 · 被引用次数：269 · 研究领域：COVID-19 and healthcare impacts、Renal and related cancers、Chronic Kidney Disease and Diabetes

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.