Cell Stem Cell
Volume 29, Issue 2, 3 February 2022, Pages 217-231.e8
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Clinical and Translational Report
SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

https://doi.org/10.1016/j.stem.2021.12.010Get rights and content
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open access

Highlights

  • 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

Summary

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.

Keywords

SARS-CoV-2
human iPSC kidney organoids
COVID-19
kidney injury
fibrosis
protease blocker
chronic kidney disease

Data and code availability

Single cell RNA sequencing data generated for this study is available from Gene Expression Omnibus (GEO): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE167747. The scripts used for pathway analyses (PROGENy and DoRothEA), ligand-receptor analysis, virus read detection (viral track), as well as the Fiji macro for fibrosis quantification in Masson’s trichrome staining are available on Zenodo: https://zenodo.org/record/5776147. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

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Senior author

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These authors contributed equally

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Present address: UniQure N.V., Amsterdam, the Netherlands

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Lead contact