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

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 stud...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2022
Materias:
Clinical and Translational Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709832/
https://www.ncbi.nlm.nih.gov/pubmed/35032430
http://dx.doi.org/10.1016/j.stem.2021.12.010
Descripción
Sumario: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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