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Binding of the virus to angiotensin\u2010converting enzyme 2 (ACE2) is an important step in the infection mechanism. However, it is unknown if ACE2 expression in patients with chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary arterial hypertension (IPAH), or pulmonary fibrosis (PF), is changed as compared to controls. We used lung samples from patients with COPD (<jats:italic>n<\/jats:italic>\u00a0=\u200928), IPAH (<jats:italic>n<\/jats:italic>\u00a0=\u200910), and PF (<jats:italic>n<\/jats:italic>\u00a0=\u200910) as well as healthy control donor (<jats:italic>n<\/jats:italic>\u00a0=\u200910) tissue samples to investigate the expression of ACE2 and related cofactors that might influence the course of SARS\u2010CoV\u20102 infection. Expression levels of the <jats:italic>ACE2<\/jats:italic> receptor, the putative receptor CD147\/<jats:italic>BSG<\/jats:italic>, and the viral entry cofactors <jats:italic>TMPRSS2<\/jats:italic> (transmembrane serine protease 2), <jats:italic>EZR<\/jats:italic>, and <jats:italic>FURIN<\/jats:italic> were determined by quantitative PCR and in open\u2010access RNA sequencing datasets. Immunohistochemical and single\u2010cell RNA sequencing (scRNAseq) analyses were used for localization and coexpression, respectively. Soluble ACE2 (sACE2) plasma levels were analyzed by enzyme\u2010linked immunosorbent assay. In COPD as compared to donor, IPAH, and PF lung tissue, gene expression of <jats:italic>ACE2<\/jats:italic>, <jats:italic>TMPRSS2<\/jats:italic>, and <jats:italic>EZR<\/jats:italic> was significantly elevated, but circulating sACE2 levels were significantly reduced in COPD and PF plasma compared to healthy control and IPAH plasma samples. Lung tissue expressions of <jats:italic>FURIN<\/jats:italic> and CD147\/<jats:italic>BSG<\/jats:italic> were downregulated in COPD. None of these changes were associated with changes in pulmonary hemodynamics. Histological analysis revealed coexpression of ACE2, TMPRSS2, and Ezrin in bronchial regions and epithelial cells. This was confirmed by scRNAseq analysis. There were no significant expression changes of the analyzed molecules in the lung tissue of IPAH and idiopathic PF as compared to control. In conclusion, we reveal increased ACE2 and TMPRSS2 expression in lung tissue with a concomitant decrease of protective sACE2 in COPD patients. These changes represent the possible risk factors for an increased susceptibility of COPD patients to SARS\u2010CoV\u20102 infection.<\/jats:p>","DOI":"10.1002\/cjp2.224","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T08:29:01Z","timestamp":1620808141000},"page":"446-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dysbalance of <scp>ACE2<\/scp> levels \u2013 a possible cause for severe <scp>COVID<\/scp>\u201019 outcome in <scp>COPD<\/scp>"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2203-2981","authenticated-orcid":false,"given":"Elisabeth","family":"Flie\u00dfer","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Lung Vascular Research  Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Birnhuber","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Lung Vascular Research  Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leigh M","family":"Marsh","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Lung Vascular Research  Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Gschwandtner","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Klepetko","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"Olschewski","sequence":"additional","affiliation":[{"name":"Division of Pulmonology Medical University of Graz  Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grazyna","family":"Kwapiszewska","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Lung Vascular Research  Graz Austria"},{"name":"Otto Loewi Research Center Medical University of Graz  Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2020.105941"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103000"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25889"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02145"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000633"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1570"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","unstructured":"Shilts J Wright GJ. 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