Human Kidney Spheroids and Monolayers Provide Insights into SARS-CoV-2 Renal Interactions.
J Am Soc Nephrol
; 32(9): 2242-2254, 2021 09.
Article
in English
| MEDLINE | ID: covidwho-1702796
ABSTRACT
BACKGROUND:
Although coronavirus disease 2019 (COVID-19) causes significan t morbidity, mainly from pulmonary involvement, extrapulmonary symptoms are also major componen ts of the disease. Kidney disease, usually presenting as AKI, is particularly severe among patients with COVID-19. It is unknown, however, whether such injury results from direct kidney infection with COVID-19's causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or from indirect mechanisms.METHODS:
Using ex vivo cell models, we sought to analyze SARS-CoV-2 interactions with kidney tubular cells and assess direct tubular injury. These models comprised primary human kidney epithelial cells (derived from nephrectomies) and grown as either proliferating monolayers or quiescent three-dimensional kidney spheroids.RESULTS:
We demonstrated that viral entry molecules and high baseline levels of type 1 IFN-related molecules were present in monolayers and kidney spheroids. Although both models support viral infection and replication, they did not exhibit a cytopathic effect and cell death, outcomes that were strongly present in SARS-CoV-2-infected controls (African green monkey kidney clone E6 [Vero E6] cultures). A comparison of monolayer and spheroid cultures demonstrated higher infectivity and replication of SARS-CoV-2 in actively proliferating monolayers, although the spheroid cultures exhibited high er levels of ACE2. Monolayers exhibited elevation of some tubular injury molecules-including molecules related to fibrosis (COL1A1 and STAT6) and dedifferentiation (SNAI2)-and a loss of cell identity, evident by reduction in megalin (LRP2). The three-dimensional spheroids were less prone to such injury.CONCLUSIONS:
SARS-CoV-2 can infect kidney cells without a cytopathic effect. AKI-induced cellular proliferation may potentially intensify infectivity and tubular damage by SARS-CoV-2, suggesting that early intervention in AKI is warranted to help minimize kidney infection.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spheroids, Cellular
/
Acute Kidney Injury
/
SARS-CoV-2
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Animals
/
Humans
Language:
English
Journal:
J Am Soc Nephrol
Journal subject:
Nephrology
Year:
2021
Document Type:
Article
Affiliation country:
Asn.2020111546
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