Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

Zou, X., Chen, K., Zou, J. et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. (2020). https://doi.org/10.1007/s11684-020-0754-0

Review written by:

Ariel Pourmorady, edited by Eunice Lee

Red - published in a lesser known general, paper only includes one type of data analysis, authors fail to deeply consider the pathophysiology of disease prior to performing their analysis

While respiratory symptoms have been a common feature among those with COVID-19, some patients are developing kidney disease and multiorgan failure, which suggest that SARS-CoV-2 may infect tissue outside the lungs. Using formerly published human scRNA-seq data (“in silico” study), Zou et al. aim to determine putative extrapulmonary targets of SARS-CoV-2 that are susceptible to infection. Analized scRNA-seq from respiratory tract (nasal mucosa, respiratory tract, bronchus, and lung), heart, digestive system (oesophagus, stomach, ilum, and liver), and the urinary system (kidney and bladder). Because ACE2 is a known receptor for SARS-CoV-2, ACE2 expression levels are used as a measure of SARS-CoV-2 susceptibility. Zou et al. began by mapping ACE2 expression among type II alveolar (AT2) cells in the lung, which are known to be infected by SARS, and possibly SARS-CoV-2. They identify that > 1% of AT2 positive cells in the lung express ACE2, and set that value as the threshold for a cell type at high risk for infection. Using scRNA-seq data from other tissue they observe the following:


Cell Types at High Risk for SARS-CoV-2 Infection (> 1% proportion of ACE2+ cells)

  • Respiratory epithelial cells (2% ACE2 cells)

  • Myocardium (7.5% ACE2 cells)

  • Ileal epithelial cells (30% ACE2 cells)

  • Esophagus (>1% ACE2 cells)

  • Proximal tubule cells of kidney (4% ACE2 cells)

  • Bladder urothelial cells (2.4% ACE2 cells)

Cell Types at Low Risk for SARS-CoV-2 Infection (< 1% proportion of ACE2+ cells)

  • Nasal and bronchial mucosa

  • Stomach

  • Liver

Review Notes
 
  • Assumes that ACE2 is the only receptor of interest.

  • Assumes that ACE2 expression is the sole determinant of infectivity, which is unlikely given the fact that levels of ACE2 expression don’t correlate with observed pathology.

  • The study conflates this paper in Nature [https://www.nature.com/articles/s41586-020-2196-x_reference.pdf]  describing observed viral load, live viral particles, and viral replication in the pharynx.

  • scRNA-seq data are taken from a variety of different sources; quality control measures are unclear.

  • “In silico” study with no “in vivo” experiments that may allow to conform some of the assumptions.

  • MInimal explanation for choice of 1% of ACE2 as determining value.

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