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Abstract: PO0835

Noninvasive Mapping of the Cellular Response to COVID-19 via Urine Single-Cell RNA Sequencing (scRNAseq)

Session Information

Category: Coronavirus (COVID-19)

  • 000 Coronavirus (COVID-19)

Authors

  • Schaub, Jennifer A., University of Michigan Health System, Ann Arbor, Michigan, United States
  • Sohaney, Ryann, University of Michigan Health System, Ann Arbor, Michigan, United States
  • Naik, Abhijit S., University of Michigan Health System, Ann Arbor, Michigan, United States
  • Menon, Rajasree, University of Michigan Health System, Ann Arbor, Michigan, United States
  • Otto, Edgar A., University of Michigan Health System, Ann Arbor, Michigan, United States
  • Mariani, Laura H., University of Michigan Health System, Ann Arbor, Michigan, United States
  • Berthier, Celine C., University of Michigan Health System, Ann Arbor, Michigan, United States
  • Kretzler, Matthias, University of Michigan Health System, Ann Arbor, Michigan, United States
Background

COVID-19 is associated with a high incidence of AKI. Mapping the transcriptional profiles of kidney and urinary track derived single cell populations can establish a framework to assess renal molecular response to COVID-19 and emerging treatment strategies.

Methods

Patients throughout the COVID-19 disease course were recruited to the study. A modification of our protocol (Arazi et al. Nat Immunol) allowed for immediate isolation of urinary cell pellets followed by 10X Genomics Chromium based scRNAseq.

Results

Urine scRNAseq data sets were generated from 13 COVID patients: age 50+/-17; 7 males; 7 African Americans; urine sampling 11 days post SARS-CoV-2 diagnosis (IQR 5-29) with 8 in AKI at time of sampling. 25,954 single cell profiles passed QC with a median of 433 cells per sample [IQR 271 to 718]). Cellular clusters were annotated to immune (9780 cells, Fig: cluster 3.-7.), renal epithelial (4364, cluster 1.) and bladder cells (4151, cluster 2.). The SARS-CoV2 receptor ACE2 was found in epithelial cells and co-expressed with CTPSL. The COVID-19 therapeutic target IL-6 was robustly detected in both myeloid and epithelial cells with co-expression networks linking IL6 expression in proximal tubular epithelial cells to HMGB1, VEGF and HIF signaling and to viral response networks in myeloid cells.

Conclusion

COVID-19 patients urine cells contain a spectrum of epithelial and immune cells expressing viral receptors of SARS-CoV-2 and therapeutic targets of emerging COVID-19 therapies offering a window to monitor renal cellular responses in COVID-19 trials.

Cell clusters from urinary pellets

Funding

  • NIDDK Support