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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.
  • Jansen J; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Pediatric Nephrology, Radboud Institute for Molecular L
  • Reimer KC; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany; Institute for Biomedical Technologies, Department of Cell Biology, RWTH Aachen University, Aachen, Germany.
  • Nagai JS; Institute for Computational Genomics, University Hospital RWTH Aachen, Germany; Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany.
  • Varghese FS; Department of Medical Microbiology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
  • Overheul GJ; Department of Medical Microbiology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
  • de Beer M; Electron Microscopy Center, Radboudumc Technology Center Microscopy, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, 6525 GA Nijmegen, the Netherlands.
  • Roverts R; Electron Microscopy Center, Radboudumc Technology Center Microscopy, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, 6525 GA Nijmegen, the Netherlands.
  • Daviran D; Electron Microscopy Center, Radboudumc Technology Center Microscopy, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, 6525 GA Nijmegen, the Netherlands.
  • Fermin LAS; Electron Microscopy Center, Radboudumc Technology Center Microscopy, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, 6525 GA Nijmegen, the Netherlands.
  • Willemsen B; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Beukenboom M; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Djudjaj S; Department of Pathology and Electron Microscopy Facility, RWTH Aachen University, Aachen, Germany.
  • von Stillfried S; Department of Pathology and Electron Microscopy Facility, RWTH Aachen University, Aachen, Germany.
  • van Eijk LE; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Mastik M; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Bulthuis M; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Dunnen WD; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • van Goor H; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Hillebrands JL; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Triana SH; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
  • Alexandrov T; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA; Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory, Hei
  • Timm MC; Department of Pathology and Electron Microscopy Facility, RWTH Aachen University, Aachen, Germany.
  • van den Berge BT; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • van den Broek M; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, the Nether
  • Nlandu Q; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Heijnert J; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Bindels EMJ; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • Hoogenboezem RM; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • Mooren F; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Kuppe C; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.
  • Miesen P; Department of Medical Microbiology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
  • Grünberg K; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Ijzermans T; Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Steenbergen EJ; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Czogalla J; Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Schreuder MF; Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, the Netherlands.
  • Sommerdijk N; Electron Microscopy Center, Radboudumc Technology Center Microscopy, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, 6525 GA Nijmegen, the Netherlands.
  • Akiva A; Electron Microscopy Center, Radboudumc Technology Center Microscopy, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, 6525 GA Nijmegen, the Netherlands.
  • Boor P; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany; Department of Pathology and Electron Microscopy Facility, RWTH Aachen University, Aachen, Germany.
  • Puelles VG; Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Floege J; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.
  • Huber TB; Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • van Rij RP; Department of Medical Microbiology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
  • Costa IG; Institute for Computational Genomics, University Hospital RWTH Aachen, Germany; Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany.
  • Schneider RK; Institute for Biomedical Technologies, Department of Cell Biology, RWTH Aachen University, Aachen, Germany; Department of Developmental Biology, Erasmus Medisch Centrum, Rotterdam, the Netherlands; Oncode Institute, Erasmus Medisch Centrum, Rotterdam, the Netherlands.
  • Smeets B; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Kramann R; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany; Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany; Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medisch Centrum, Rotterdam, the Netherlan
Cell Stem Cell ; 29(2): 217-231.e8, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1586459
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Long Covid Limits: Humans Language: English Journal: Cell Stem Cell Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Long Covid Limits: Humans Language: English Journal: Cell Stem Cell Year: 2022 Document Type: Article