Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations

JCI Insight. 2021 Dec 22;6(24):e154882. doi: 10.1172/jci.insight.154882.


Kidneys are critical target organs of COVID-19, but susceptibility and responses to infection remain poorly understood. Here, we combine SARS-CoV-2 variants with genome-edited kidney organoids and clinical data to investigate tropism, mechanism, and therapeutics. SARS-CoV-2 specifically infects organoid proximal tubules among diverse cell types. Infections produce replicating virus, apoptosis, and disrupted cell morphology, features of which are revealed in the context of polycystic kidney disease. Cross-validation of gene expression patterns in organoids reflects proteomic signatures of COVID-19 in the urine of critically ill patients indicating interferon pathway upregulation. SARS-CoV-2 viral variants alpha, beta, gamma, kappa, and delta exhibit comparable levels of infection in organoids. Infection is ameliorated in ACE2-/- organoids and blocked via treatment with de novo-designed spike binder peptides. Collectively, these studies clarify the impact of kidney infection in COVID-19 as reflected in organoids and clinical populations, enabling assessment of viral fitness and emerging therapies.

Keywords: COVID-19; Genetic diseases; Molecular pathology; Nephrology; iPS cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / urine*
  • Adult
  • Aged
  • Angiotensin-Converting Enzyme 2 / genetics
  • Animals
  • Apoptosis
  • Bowman Capsule / cytology
  • Bowman Capsule / virology
  • COVID-19 / complications
  • COVID-19 / urine*
  • Chlorocebus aethiops
  • Female
  • Gene Knockout Techniques
  • Hospital Mortality
  • Hospitalization
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / virology*
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Kidney Tubules, Proximal / virology*
  • Male
  • Middle Aged
  • Organoids / metabolism
  • Organoids / virology*
  • Podocytes / virology
  • Polycystic Kidney Diseases
  • Protein Kinase D2 / genetics
  • Proteome
  • Receptors, Coronavirus / genetics
  • Reproducibility of Results
  • SARS-CoV-2 / pathogenicity*
  • Transcriptome
  • Vero Cells
  • Viral Tropism
  • Virus Replication


  • Protein Kinase D2
  • Proteome
  • Receptors, Coronavirus
  • Angiotensin-Converting Enzyme 2

Supplementary concepts

  • SARS-CoV-2 variants