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.
Keywords: COVID-19; SARS-CoV-2; acute kidney injury; acute kidney injury and ICU nephrology; basic science; single-cell RNA sequencing; urine.
【저자키워드】 COVID-19, SARS-CoV-2, Acute kidney injury, Single-cell RNA sequencing, Urine, Basic science, acute kidney injury and ICU nephrology, TMPRSS2, 【초록키워드】 ACE2, Gene Expression, Mortality, Anti-inflammatory, Antiviral, severity, Acute kidney injury, hospitalized patients, Pathway analysis, ICU, Single-cell RNA sequencing, RNA, kidney, AKI, pathophysiology, cells, Patient, pathway, Urine, immune cells, dataset, Kidney diseases, information, resource, single-cell, cellular, Evidence, Hypothesis, Analysis, Basic science, SARS-CoV-2 viral RNA, Pathways, evidence of, cell types, cell type, Non-COVID-19, Urinary bladder, enrichment, alteration, one patient, TMPRSS2 expression, transcripts, direct infection, preliminary evidence, bladder, scRNAseq, transcript, Cell, urinary sediment, highest, tested, performed, collected, include, eight, contribute, occur, hospitalized patient, acute kidney, infection with SARS-CoV-2, patients with AKI, tubular cell, uninjured, with COVID-19, 【제목키워드】 RNA, AKI, Diversity, urinary,