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Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p\u2009=\u20090.042) and bronchial biopsies (0.23, p\u2009=\u20090.050), and correlated with worse lung function (r\u2009=\u2009\u2212\u20090.28, p\u2009=\u20090.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p\u2009=\u20090.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p\u2009=\u20090.0034), having cardiovascular disease (0.23, p\u2009=\u20090.048) or hypertension (0.34, p\u2009=\u20090.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p\u2009=\u20090.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of \u20130.26 (p\u2009=\u20090.033) and \u2212\u20090.40, (p\u2009=\u20090.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p\u2009=\u20090.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p\u2009=\u20090.0040), and bronchial biopsies, (log2FC of 0.18 (p\u2009=\u20090.017), in COPD vs HV-ES.<\/jats:p><jats:p>Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p\u2009=\u20090.0012) and log2FC of 0.56 (p\u2009=\u20095.49E\u221206), respectively) and bronchial biopsies (log2FC of 0.49 (p\u2009=\u20090.00021) and log2FC of 0.246 (p\u2009=\u20090.028), respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12931-021-01755-3","type":"journal-article","created":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T07:05:01Z","timestamp":1622271901000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Dysregulation of COVID-19 related gene expression in the COPD lung"],"prefix":"10.1186","volume":"22","author":[{"name":"the MICA II Studygroup","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair","family":"Watson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"\u00d6berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Angermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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