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Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Expression of ACE2 and TMPRSS2, the SARS2-CoV-2 receptor and co-receptor, in prostate epithelial cells

    Authors: Hanbing Song; Bobak Seddighzadeh; Matthew R Cooperberg; Franklin W Huang

    doi:10.1101/2020.04.24.056259 Date: 2020-04-25 Source: bioRxiv

    The COVID-19 pandemic has spread across more than 200 countries and resulted in over 170,000 deaths. For unclear reasons, higher mortality rates from COVID-19 have been reported in men compared to women. While the SARS-CoV-2 receptor ACE2 and serine protease TMPRSS2 have been detected in lung and other tissues, it is not clear what sex differences may exist. We analyzed a publicly-available normal human prostate single-cell RNA sequencing dataset and found TMPRSS2 and ACE2 co-expressing cells in epithelial cells, with a higher proportion in club HP and hillock cells. Then we investigated datasets of lung epithelial cells and also found club HP cells co-expressing TMPRSS2 and ACE2. A comparison of ACE2 expression in lung tissue between males TRANS and females TRANS showed higher expression in males TRANS and a larger proportion of ACE2+ cells in male TRANS type II pneumocytes, with preliminary evidence that type II pneumocytes of all lung epithelial cell types showed the highest expression of ACE2. These results raise the possibility that sex differences in ACE2 expression and the presence of double-positive cells in the prostate may contribute to the observed disparities of COVID-19.

    Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

    Authors: Harlan Barker; Seppo Parkkila

    doi:10.1101/2020.04.13.038752 Date: 2020-04-13 Source: bioRxiv

    The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 than any other organ. The large intestine, kidney and testis showed moderate signals, whereas the signal was weak in the lung. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club HP, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/ blood SERO vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene. Our results also confirmed that age TRANS and gender TRANS play no significant role in the regulation of ACE2 mRNA expression in the lung. IMPORTANCEVaccines and new medicines are urgently needed to prevent spread of COVID-19 pandemic, reduce the symptoms, shorten the duration of disease, prevent virus spread in the body, and most importantly to save lives. One of the key drug targets could be angiotensin-converting enzyme 2 (ACE2), which is a crucial receptor for the corona virus (SARS-CoV-2). It is known that SARS coronavirus infections lead to worse outcome in the elderly TRANS and in males TRANS. Therefore, one aim of the present study was to investigate whether age TRANS or sex could contribute to the regulation of ACE2 expression. We also decided to explore the transcriptional regulation of ACE2 gene expression. Since data on ACE2 distribution is still conflicting, we aimed to get a more comprehensive view of the cell types expressing the receptor of SARS-CoV-2. Finally, we studied the coexpression of ACE2 with other genes and explored its putative functions using gene ontology enrichment analysis.

    A Hint on the COVID-19 Risk: Population Disparities in Gene Expression of Three Receptors of SARS-CoV MESHD

    Authors: Guoshuai Cai; Xiang Cui; Xia Zhu; Jun Zhou

    id:10.20944/preprints202002.0408.v1 Date: 2020-02-27 Source: Preprints.org

    The current spreading novel coronavirus SARS-CoV-2 is highly infectious and pathogenic and has attracted global attention. Recent studies have found that SARS-CoV-2 and SARS-CoV share around 80% of homology and use the same cell entry receptor, ACE2. These inspired us to study other receptors of SARS-CoV MESHD, which may be used for SARS-CoV-2 binding as well. In this study, we screened the gene expression of three receptors (ACE2, DC-SIGN and L-SIGN) in four datasets of normal lung tissue from lung adenocarcinoma HP patients and two single-cell RNA sequencing datasets from normal lung and bronchial epithelial cells separately. No significant difference in gene expression of these three receptors were found between gender TRANS groups ( male TRANS vs female TRANS). We found higher gene expression of DC-SIGN in elder with age TRANS>60 and higher gene expression of L-SIGN in Caucasian than Asian. Similar to ACE2, we observed significantly higher DC-SIGN gene expression in the lungs of smokers, especially former smokers. However, smokers upregulate ACE2 and DC-SIGN gene expression in different cell types. In the whole lung, ACE2 is actively expressed in remodeled Alveolar Type II MESHD cells of former smokers, while DC-SIGN is largely expressed in monocytes of former smokers and dendritic cells of current smokers. In bronchial epithelium, no obvious gene expression of DC-SIGN and L-SIGN was observed while ACE2 was found to be actively expressed in goblet cells of current smokers and club HP cells of non-smokers. In conclusion, our findings may indicate that smokers, especially former smokers, and people over 60 have higher risk and are more susceptible to SARS-CoV-2 infection MESHD. Also, this study provides hints on possible SARS-CoV-2 pathogenicity mechanisms in lung infection MESHD.

    Tobacco-use disparity in gene expression of ACE2, the receptor of 2019-nCov

    Authors: Guoshuai Cai

    doi:10.1101/2020.02.05.20020107 Date: 2020-02-11 Source: medRxiv

    In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age TRANS, gender TRANS and smoking status in ACE2 gene expression and its distribution among cell types. We didn't find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups TRANS (>60 vs <60) or gender TRANS groups ( male TRANS vs female TRANS). However, we observed significantly higher ACE2 gene expression in former smoker's lung compared to non-smoker's lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club HP cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection MESHD paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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