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).
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
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.