Journal
CELL STEM CELL
Volume 29, Issue 2, Pages 217-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2021.12.010
Keywords
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Categories
Funding
- German Research Foundation [DFG: KR 4073/11-1, SFBTRR219, 322900939, CRU344, 428857858, CRU5011 InteraKD 445703531]
- European Research Council [ERC-StG 677448]
- Federal Ministry of Research and Education [BMBF NUM-COVID19, Organo-Strat 01KX2021]
- Dutch Kidney Foundation (DKF) TASK FORCE consortium [CP1805]
- Else Kroener Fresenius Foundation [2017_A144]
- ERA-CVD MENDAGE consortium [BMBF 01KL1907]
- DFG [CRU 344, CRU344 P2]
- BMBF eMed Consortium Fibromap
- KWF Kankerbestrijding [11031/2017-1]
- ERC (deFiber) [ERC-StG 757339]
- Netherlands Organisation for Scientific Research (NWO) [091 501 61 81 01 36]
- DKF [19OK005, 14A3D104, DJ100/1-1]
- NWO [016.156.363, VI.Veni.192.094]
- NWO VICI [16.VICI.170.090]
- BMBF (DEFEAT PANDEMIcs) [01KX2021]
- Federal Ministry of Health (German Registry for COVID-19 Autopsies-DeRegCOVID, www.DeRegCOVID.ukaachen.de) [ZMVI1-2520COR201]
- German Research Foundation (DFG) [322900939, SFB/TRR219, 454024652]
- VGP
- TBH [SFB1192]
- ERC Advanced Investigator grant [H2020-ERC-2017-ADV-788982-COLMIN]
- Kioa L. Wijnsma (Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Amalia Children's Hospital, Radboud UniversityMedicalCenter)
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The study found that SARS-CoV-2 can directly infect kidney cells, leading to cell injury and fibrosis, causing kidney failure. Inhibitors can alleviate the infection.
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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