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SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids
Ist Teil von
Cell stem cell, 2022-02, Vol.29 (2), p.217-231.e8
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2022
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
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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•COVID-19 patients present tubulo-interstitial kidney fibrosis compared with controls•SARS-CoV-2 infection stimulates profibrotic signaling in human kidney organoids•SARS-CoV-2 infection can be inhibited by a protease blocker in human kidney organoids
Jansen, Reimer, Nagai, et al. report that SARS-CoV-2 infects kidney cells and is associated with kidney fibrosis in patients. Using single-cell transcriptomics of infected kidney organoids, they show that SARS-CoV-2 causes kidney injury and stimulates profibrotic signaling. Viral infection in organoids was inhibited by a recently developed protease blocker.