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      Angiotensin-converting enzyme 2 expression in COPD and IPF fibroblasts: the forgotten cell in COVID-19

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          Abstract

          The COVID-19 pandemic is associated with severe pneumonia and acute respiratory distress syndrome leading to death in susceptible individuals. For those who recover, post-COVID-19 complications may include development of pulmonary fibrosis. Factors contributing to disease severity or development of complications are not known. Using computational analysis with experimental data, we report that idiopathic pulmonary fibrosis (IPF)- and chronic obstructive pulmonary disease (COPD)-derived lung fibroblasts express higher levels of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 entry and part of the renin-angiotensin system that is antifibrotic and anti-inflammatory. In preclinical models, we found that chronic exposure to cigarette smoke, a risk factor for both COPD and IPF and potentially for SARS-CoV-2 infection, significantly increased pulmonary ACE2 protein expression. Further studies are needed to understand the functional implications of ACE2 on lung fibroblasts, a cell type that thus far has received relatively little attention in the context of COVID-19.

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          Most cited references28

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          Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

          In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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            Is Open Access

            A pneumonia outbreak associated with a new coronavirus of probable bat origin

            Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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              Is Open Access

              SCANPY : large-scale single-cell gene expression data analysis

              Scanpy is a scalable toolkit for analyzing single-cell gene expression data. It includes methods for preprocessing, visualization, clustering, pseudotime and trajectory inference, differential expression testing, and simulation of gene regulatory networks. Its Python-based implementation efficiently deals with data sets of more than one million cells (https://github.com/theislab/Scanpy). Along with Scanpy, we present AnnData, a generic class for handling annotated data matrices (https://github.com/theislab/anndata).
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                Author and article information

                Journal
                Am J Physiol Lung Cell Mol Physiol
                Am J Physiol Lung Cell Mol Physiol
                ajplung
                Am J Physiol Lung Cell Mol Physiol
                AJPLUNG
                American Journal of Physiology - Lung Cellular and Molecular Physiology
                American Physiological Society (Bethesda, MD )
                1040-0605
                1522-1504
                1 January 2021
                28 October 2020
                28 October 2020
                : 320
                : 1
                : L152-L157
                Affiliations
                [1] 1Research Institute of the McGill University Health Centre , Montreal, Quebec, Canada
                [2] 2Department of Pathology, McGill University , Montreal, Quebec, Canada
                [3] 3Department of Medicine, McGill University , Montreal, Quebec, Canada
                [4] 4Department of Pharmacology and Therapeutics, McGill University , Montreal, Quebec, Canada
                [5] 5Department of Computational Biology, Carnegie Mellon University , Pittsburgh, Pennsylvania
                [6] 6Department of Medicine, McMaster University & St. Joseph’s Healthcare , Hamilton, Ontario, Canada
                [7] 7Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan
                Author notes
                Correspondence: C. J. Baglole ( Carolyn.baglole@ 123456mcgill.ca ).
                Author information
                https://orcid.org/0000-0001-5183-6885
                https://orcid.org/0000-0002-2090-6331
                Article
                L-00455-2020 L-00455-2020
                10.1152/ajplung.00455.2020
                7869954
                33112187
                e6671363-9d12-49d1-8433-9565956fdb3c
                Copyright © 2021 the American Physiological Society
                History
                : 22 September 2020
                : 15 October 2020
                : 16 October 2020
                Funding
                Funded by: Gouvernement du Canada | CIHR | Institute of Health Services and Policy Research (IHSPR) 10.13039/501100000037
                Award Recipient : Carolyn J Baglole
                Funded by: Canada Foundation for Innovation (Fondation canadienne pour l'innovation) 10.13039/501100000196
                Award Recipient : Carolyn J Baglole
                Funded by: Fonds de Recherche du Québec-Société et Culture (FRQSC) 10.13039/100008240
                Award Recipient : Carolyn J Baglole
                Funded by: Taibah University 10.13039/501100002403
                Award Recipient : Noof Aloufi
                Categories
                Rapid Report
                The Pathophysiology of COVID-19 and SARS-CoV-2 Infection
                Custom metadata
                True

                Anatomy & Physiology
                ace2,copd,fibroblast,ipf,sars-cov-2
                Anatomy & Physiology
                ace2, copd, fibroblast, ipf, sars-cov-2

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