Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations.
JCI Insight
; 6(24)2021 12 22.
Article
in English
| MEDLINE | ID: covidwho-1518199
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Organoids
/
Acute Kidney Injury
/
SARS-CoV-2
/
COVID-19
/
Kidney
/
Kidney Tubules, Proximal
Type of study:
Prognostic study
/
Randomized controlled trials
Topics:
Long Covid
/
Variants
Language:
English
Year:
2021
Document Type:
Article
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