Figure 8.

Study overview. To understand how the kidney may be affected by COVID-19, we performed spatial, systems, and clinical association analyses of ACE2 and other SARS-CoV-2 host factors in kidney biopsies from living donors (LD) and Pima Indians with DKD and kidney cells isolated from the urine of hospitalized COVID-19 patients (COV). A: Biopsy samples from those with DKD and living donors were processed for in situ hybridization (ISH) and single-cell RNA sequencing (RNAseq) profiling. Single-cell RNA sequencing of kidney tissue from living donors and DKD patients and urine cell pellets from samples of COVID-19 patients were analyzed for determination of cell type expression specificity of ACE2 in healthy and disease states. B: For each single-cell RNA sequencing data set, ACE2+ differential expression signatures were identified. C: Associations of ACE2 expression levels in DKD with clinical characteristics were evaluated, including exposure to renin-angiotensin-aldosterone system (RAAS) blockers and ACE inhibitors. D: Expression of ACE2 and key proteases between living donor and DKD proximal tubule epithelial cells was compared. E: ACE2 expression signatures across data sets identified aspects induced in proximal tubule epithelial cells expressing ACE2 in DKD samples in comparison with samples of living donors. These gene sets significantly overlapped those reported to be affected by direct SARS-CoV-2 infection. F: The biological processes in ACE2+ expression signatures were characterized by projecting these signature genes onto proximal tubule epithelial cells–specific functional networks at HumanBase (https://hb.flatironinstitute.org/covid-kidney). These networks represent genes and their interactions in biological processes and pathways active in PTECs. Adapted with permission from Menon et al. (84).