SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids
Jansen J., Reimer KC., Nagai JS., Varghese FS., Overheul GJ., de Beer M., Roverts R., Daviran D., Fermin LAS., Willemsen B., Beukenboom M., Djudjaj S., von Stillfried S., van Eijk LE., Mastik M., Bulthuis M., Dunnen WD., van Goor H., Hillebrands JL., Triana SH., Alexandrov T., Timm MC., van den Berge BT., van den Broek M., Nlandu Q., Heijnert J., Bindels EMJ., Hoogenboezem RM., Mooren F., Kuppe C., Miesen P., Grünberg K., Ijzermans T., Steenbergen EJ., Czogalla J., Schreuder MF., Sommerdijk N., Akiva A., Boor P., Puelles VG., Floege J., Huber TB., Achdout H., Aimon A., Bar-David E., Barr H., Ben-Shmuel A., Bennett J., Boby ML., Borden B., Bowman GR., Brun J., BVNBS S., Calmiano M., Carbery A., Cattermole E., Chernychenko E., Choder JD., Clyde A., Coffland JE., Cohen G., Cole J., Contini A., Cox L., Cvitkovic M., Dias A., Donckers K., Dotson DL., Douangamath A., Duberstein S., Dudgeon T., Dunnett L., Eastman PK., Erez N., Eyermann CJ., Fairhead M., Fate G., Fearon D., Federov O., Ferla M., Fernandes RS., Ferrins L., Foster R., Foster H., Gabizon R., Garcia-Sastre A., Gawriljuk VO., Gehrtz P., Gileadi C., Giroud C., Glass WG., Glen R., Itai glinert None., Godoy AS., Gorichko M., Gorrie-Stone T., Griffen EJ., Hart SH., Heer J., Henry M.
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.