TY - JOUR
T1 - SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids
AU - The COVID Moonshot consortium
AU - Jansen, Jitske
AU - Reimer, Katharina C.
AU - Nagai, James S.
AU - Varghese, Finny S.
AU - Overheul, Gijs J.
AU - de Beer, Marit
AU - Roverts, Rona
AU - Daviran, Deniz
AU - Fermin, Liline A.S.
AU - Willemsen, Brigith
AU - Beukenboom, Marcel
AU - Djudjaj, Sonja
AU - von Stillfried, Saskia
AU - van Eijk, Larissa E.
AU - Mastik, Mirjam
AU - Bulthuis, Marian
AU - Dunnen, Wilfred den
AU - van Goor, Harry
AU - Hillebrands, Jan Luuk
AU - Triana, Sergio H.
AU - Alexandrov, Theodore
AU - Timm, Marie Cherelle
AU - van den Berge, Bartholomeus T.
AU - van den Broek, Martijn
AU - Nlandu, Quincy
AU - Heijnert, Joelle
AU - Bindels, Eric M.J.
AU - Hoogenboezem, Remco M.
AU - Mooren, Fieke
AU - Kuppe, Christoph
AU - Miesen, Pascal
AU - Grünberg, Katrien
AU - Ijzermans, Ties
AU - Steenbergen, Eric J.
AU - Czogalla, Jan
AU - Schreuder, Michiel F.
AU - Sommerdijk, Nico
AU - Akiva, Anat
AU - Boor, Peter
AU - Puelles, Victor G.
AU - Floege, Jürgen
AU - Huber, Tobias B.
AU - Achdout, Hagit
AU - Aimon, Anthony
AU - Bar-David, Elad
AU - Barr, Haim
AU - Ben-Shmuel, Amir
AU - Bennett, James
AU - Boby, Melissa L.
AU - Voelz, Vincent
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2022/2/3
Y1 - 2022/2/3
N2 - 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.
AB - 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.
KW - COVID-19
KW - SARS-CoV-2
KW - chronic kidney disease
KW - fibrosis
KW - human iPSC kidney organoids
KW - kidney injury
KW - protease blocker
UR - http://www.scopus.com/inward/record.url?scp=85123016842&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2021.12.010
DO - 10.1016/j.stem.2021.12.010
M3 - Article
C2 - 35032430
AN - SCOPUS:85123016842
SN - 1934-5909
VL - 29
SP - 217-231.e8
JO - Cell stem cell
JF - Cell stem cell
IS - 2
ER -
