@article{10.1172/jci.insight.154882, author = {Louisa Helms AND Silvia Marchiano AND Ian B. Stanaway AND Tien-Ying Hsiang AND Benjamin A. Juliar AND Shally Saini AND Yan Ting Zhao AND Akshita Khanna AND Rajasree Menon AND Fadhl Alakwaa AND Carmen Mikacenic AND Eric D. Morrell AND Mark M. Wurfel AND Matthias Kretzler AND Jennifer L. Harder AND Charles E. Murry AND Jonathan Himmelfarb AND Hannele Ruohola-Baker AND Pavan K. Bhatraju AND Michael Gale Jr. AND Benjamin S. Freedman}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations}, year = {2021}, month = {12}, volume = {6}, url = {https://insight.jci.org/articles/view/154882}, abstract = {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.}, number = {24}, doi = {10.1172/jci.insight.154882}, url = {https://doi.org/10.1172/jci.insight.154882}, }