TY - JOUR
KW - Acute Kidney Injury
KW - Adult
KW - Aged
KW - Angiotensin-Converting Enzyme 2
KW - Animals
KW - Apoptosis
KW - Bowman Capsule
KW - COVID-19
KW - Chlorocebus aethiops
KW - Female
KW - Gene Knockout Techniques
KW - Genetic diseases
KW - Hospital Mortality
KW - Hospitalization
KW - Humans
KW - kidney
KW - Kidney Tubules, Proximal
KW - Male
KW - Middle Aged
KW - Molecular pathology
KW - Nephrology
KW - organoids
KW - Podocytes
KW - Polycystic Kidney Diseases
KW - Protein Kinase D2
KW - Proteome
KW - Receptors, Coronavirus
KW - Reproducibility of Results
KW - SARS-CoV-2
KW - Transcriptome
KW - Vero Cells
KW - Viral Tropism
KW - Virus Replication
KW - iPS cells
AU - Louisa Helms
AU - Silvia Marchiano
AU - Ian B. Stanaway
AU - Tien-Ying Hsiang
AU - Benjamin A. Juliar
AU - Shally Saini
AU - Yan Ting Zhao
AU - Akshita Khanna
AU - Rajasree Menon
AU - Fadhl Alakwaa
AU - Carmen Mikacenic
AU - Eric D. Morrell
AU - Mark M. Wurfel
AU - Matthias Kretzler
AU - Jennifer L. Harder
AU - Charles E. Murry
AU - Jonathan Himmelfarb
AU - Hannele Ruohola-Baker
AU - Pavan K. Bhatraju
AU - Michael Gale
AU - Benjamin S. Freedman
AB - 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.
BT - JCI insight
DA - 2021-12-22
DO - 10.1172/jci.insight.154882
IS - 24
LA - eng
N2 - 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.
PY - 2021
EP - e154882
T2 - JCI insight
TI - Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations
VL - 6
SN - 2379-3708
ER -