Single-Cell RNA Sequencing of Urinary Cells Reveals Distinct Cellular Diversity in COVID-19–Associated AKI
Matthew D. Cheung, Elise N. Erman, Shanrun Liu, Nathaniel Erdmann, Gelare Ghajar-Rahimi, Kyle H. Moore, Jeffrey C. Edberg, James F. George, Anupam Agarwal
Abstract
Background AKI is a common sequela of infection with SARS-CoV-2 and contributes to the severity and mortality from COVID-19. Here, we tested the hypothesis that kidney alterations induced by COVID-19–associated AKI could be detected in cells collected from urine. Methods We performed single-cell RNA sequencing (scRNAseq) on cells recovered from the urine of eight hospitalized patients with COVID-19 with ( n =5) or without AKI ( n =3) as well as four patients with non–COVID-19 AKI ( n =4) to assess differences in cellular composition and gene expression during AKI. Results Analysis of 30,076 cells revealed a diverse array of cell types, most of which were kidney, urothelial, and immune cells. Pathway analysis of tubular cells from patients with AKI showed enrichment of transcripts associated with damage-related pathways compared with those without AKI. ACE2 and TMPRSS2 expression was highest in urothelial cells among cell types recovered. Notably, in one patient, we detected SARS-CoV-2 viral RNA in urothelial cells. These same cells were enriched for transcripts associated with antiviral and anti-inflammatory pathways. Conclusions We successfully performed scRNAseq on urinary sediment from hospitalized patients with COVID-19 to noninvasively study cellular alterations associated with AKI and established a dataset that includes both injured and uninjured kidney cells. Additionally, we provide preliminary evidence of direct infection of urinary bladder cells by SARS-CoV-2. The urinary sediment contains a wealth of information and is a useful resource for studying the pathophysiology and cellular alterations that occur in kidney diseases.