The scRNA-seq Expression Profiling of the Receptor ACE2 and the Cellular Protease TMPRSS2 Reveals Human Organs Susceptible to SARS-CoV-2 Infection.

Jing Qi,Liying Zhang,Shuilin Jin,Zicen Zhao,Beibei Liu,Jiao Hua,Jialin Bian,Yang Zhou

doi:10.3390/ijerph18010284

Jing Qi, Liying Zhang + Show 6 more

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https://doi.org/10.3390/ijerph18010284

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Abstract

COVID-19 patients always develop multiple organ dysfunction syndromes other than lungs, suggesting the novel virus SARS-CoV-2 also invades other organs. Therefore, studying the viral susceptibility of other organs is important for a deeper understanding of viral pathogenesis. Angiotensin-converting enzyme II (ACE2) is the receptor protein of SARS-CoV-2, and TMPRSS2 promotes virus proliferation and transmission. We investigated the ACE2 and TMPRSS2 expression levels of cell types from 31 organs to evaluate the risk of viral infection using single-cell RNA sequencing (scRNA-seq) data. For the first time, we found that the gall bladder and fallopian tube are vulnerable to SARS-CoV-2 infection. Besides, the nose, heart, small intestine, large intestine, esophagus, brain, testis, and kidney are also identified to be high-risk organs with high expression levels of ACE2 and TMPRSS2. Moreover, the susceptible organs are grouped into three risk levels based on the ACE2 and TMPRSS2 expression. As a result, the respiratory system, digestive system, and urinary system are at the top-risk level for SARS-CoV-2 infection. This study provides evidence for SARS-CoV-2 infection in the human nervous system, digestive system, reproductive system, respiratory system, circulatory system, and urinary system using scRNA-seq data, which helps in the clinical diagnosis and treatment of patients.

Highlights

IntroductionDisease 2019 (COVID-19) by the World Health Organization (WHO) [1], was first reported in several patients in Wuhan, China [2,3,4,5]
AT2 cells contain an average of 0.79% ACE2expressed cells and 21.20% TMPRSS2-expressed cells across eight samples (Figure 1A,B, Supplementary File: Figures S1–S8, and Table 2), and the expression levels of ACE2 and TMPRSS2 are high in AT2 cells (Figure 1C,D)
The results show that the heart is a susceptible organ, indicating that SARS-CoV-2 may affect the normal operation of the cardiovascular system

Summary

Introduction

Disease 2019 (COVID-19) by the World Health Organization (WHO) [1], was first reported in several patients in Wuhan, China [2,3,4,5]. As of December 2020, COVID-19 has spread widely in more than 200 countries; more than 71.43 million people have suffered from the disease, and over 1.6 million people have died, posing a major threat to global public health. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) [1,6,7], which seriously damages the respiratory system. Patients develop acute respiratory infection symptoms, and even acute respiratory distress syndrome (ARDS), acute respiratory failure, and other severe symptoms [4,5,8,9]. SARS-CoV-2 enters the cell via the binding of spike (S) protein and angiotensin-converting enzyme

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