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 AS; 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 MJ; 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; COVID Moonshot consortium,; van Rij, Ronald P; Costa, Ivan G; Schneider, Rebekka K; Smeets, Bart; Kramann, Rafael; De Jonghe, Steven; Jochmans, Dirk; Neyts, Johan

doi:10.1016/j.stem.2021.12.010

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

Author:

Jansen, Jitske

Reimer, Katharina C ; Nagai, James S ; Varghese, Finny S ; Overheul, Gijs J ; de Beer, Marit ; Roverts, Rona ; Daviran, Deniz ; Fermin, Liline AS ; 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 MJ ; 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 ; COVID Moonshot consortium, ; van Rij, Ronald P ; Costa, Ivan G ; Schneider, Rebekka K ; Smeets, Bart ; Kramann, Rafael ; De Jonghe, Steven ; Jochmans, Dirk ; Neyts, Johan

Keywords:

COVID-19, Fibrosis, Humans, Kidney, Organoids, Post-Acute COVID-19 Syndrome, SARS-CoV-2, chronic kidney disease, fibrosis, human iPSC kidney organoids, kidney injury, protease blocker, Science & Technology, Life Sciences & Biomedicine, Cell & Tissue Engineering, Cell Biology, TRANSCRIPTION FACTOR, GENE-EXPRESSION, CHOROID-PLEXUS, INJURY, ORIGIN, CELLS, MYOFIBROBLASTS, RECONSTRUCTION, PROGENITORS, MECHANISMS, COVID Moonshot consortium, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

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.