SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids.
JANSEN, Jitske; FERNANDES, Rafaela Sachetto; OLIVEIRA, Victor Gawriljuk Ferraro; GODOY, Andre Schutzer de; NAKAMURA, Aline Minali; NOSKE, Gabriela Dias; OLIVA, Glaucius.
JANSEN, Jitske; FERNANDES, Rafaela Sachetto; OLIVEIRA, Victor Gawriljuk Ferraro; GODOY, Andre Schutzer de; NAKAMURA, Aline Minali; NOSKE, Gabriela Dias; OLIVA, Glaucius.
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 stemcell-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.
@article={003081076,author = {JANSEN, Jitske; FERNANDES, Rafaela Sachetto; OLIVEIRA, Victor Gawriljuk Ferraro; GODOY, Andre Schutzer de; NAKAMURA, Aline Minali; NOSKE, Gabriela Dias; OLIVA, Glaucius.},title={SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids},journal={Cell Stem Cell},note={v. 29, n. 2, p. 217-231 + e1-e8},year={2022}}