The scRNA-seq expression profiling of the receptor ACE2 and the cellular protease TMPRSS2 reveals human organs susceptible to COVID-19 infection

Abstract

SummaryBackgroundCOVID-19 caused by SARA-CoV-2 is a disaster sweeping over 200 countries, and more than 2,150,000 people are suffering from the disease and 140,000 people died. ACE2 is a receptor protein of SARS- CoV-2, and TMPRSS2 promotes virus proliferation and transmission. Some patients developed multiple organ dysfunction syndromes other than lungs. Therefore, studying the viral susceptibility of other organs is important for a deeper understanding of viral pathogenesis.MethodsThe advantage of scRNA-seq data is the identification of cell types by clustering the gene expression of cells. ACE2 and TMPRSS2 are highly expressed in AT2 of lungs, we compared the ACE2 and TMPRSS2 expression levels of cell types from 31 organs, with AT2 of lungs to evaluate the risk of the viral infection using scRNA-seq data.FindingsFor the first time, we found the brain, gall bladder, and fallopian tube are vulnerable to COVID-19 infection. Besides, the nose, heart, small intestine, large intestine, esophagus, 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 TMPRSS2 expression. As a result, the respiratory system, digestive system and reproductive system are at the top-risk level to COVID-19 infection.InterpretationThis study provides evidence for COVID-19 infection in the human nervous system, digestive system, reproductive system, respiratory system, circulatory system and urinary system using scRNA-seq data, which helps for the clinical diagnosis and treatment of patients.

The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission

“…The serine protease TMPRSS2 on the cell surface activates the spike proteinmediated membrane fusion pathway, which is important for virus spread (Iwata-Yoshikawa et al, 2019;Zhou et al, 2015). It has been reported that TMPRSS2 is enriched in nasal and bronchial tissues (Qi et al, 2020;Sungnak et al, 2020a;Sungnak et al, 2020b), implying that the transmission of SARS-CoV-2 by respiratory droplets might be enhanced for virus bearing an intact versus a deleted S1/S2 boundary. In our hamster experiments, the deletion mutant virus Sdel exhibited decreased viral infection and disease compared to Sfull.…”

Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors Driving Pathogenesis of SARS-CoV-2

“…Indeed, expression of ACE2 and TMPRSS2 have been detected in lung airway cells and the upper respiratory epithelium, the primary site of SARS-CoV-2 action (Sungnak et al, 2020;Ziegler et al, 2020). Beyond respiratory distress, some patients with SARS-CoV-2 viremia develop multiple organ injuries, and cells of these tissues also express ACE2 and TMPRSS2 (Qi et al, 2020;Seow et al, 2020;Zou et al, 2020).…”

Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system

“…Again similar to SARS-CoV, SARS-CoV-2 also requires the transmembrane serine protease 2 (TMPRSS2) for spike protein priming and entry into the host cell [22], although for SARS-COV-2 this might vary depending on the cell type [24,25]. Therefore, cells that express ACE2 and TMPRSS2, such as the glia and neurons, would be plausible targets for SARS-CoV-2 infection [26]. At these early stages of our understanding of COVID-19, SARS-CoV-2 infection of the CNS is speculative and, although the mechanisms of SARS-CoV-2 entry into the CNS have not yet been studied, extrapolation from closely related viruses points toward some possible routes of infection.…”