{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T13:41:34Z","timestamp":1778938894925,"version":"3.51.4"},"reference-count":42,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Introduction:<\/i><\/b> Since angiotensin converting enzyme-2 (ACE2) was discovered as an essential entry factor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), there has been conflicting evidence regarding the role of renin-angiotensin-aldosterone system (RAAS) in COVID-19. This study elucidates pulmonary expression patterns SARS-CoV-2 entry factors (ACE2 and transmembrane protease serine subtype 2, TMPRSS2) and RAAS components in lethal COVID-19. <b><i>Methods:<\/i><\/b> Lung tissue from COVID-19 autopsies (<i>n<\/i> = 27) and controls (<i>n<\/i> = 23) underwent immunohistochemical staining for RAAS components (angiotensin receptors 1 and 2, ACE2 and Mas-receptor) and bradykinin receptors 1 and 2. Staining of individual cellular populations (alveolar pneumocytes [ALV], desquamated cells [DES] and endothelium [END]) was measured by a binary scale (positive\/negative). SARS-CoV-2 was detected using immunohistochemistry against nucleocapsid protein, <i>in-situ<\/i> hybridization and quantitative reverse transcriptase polymerase chain reaction. Gene expression profiling for <i>ACE2, ACE<\/i> and <i>TMPRSS2<\/i> was performed. <b><i>Results:<\/i><\/b> Subtle differences were observed when comparing COVID-19 patients and controls not reaching statistical significance, such as a higher incidence of ACE2-positivity in END (52% vs. 39%) but lower positivity in ALVs (63% vs. 70%) and an overall downregulation of <i>ACE2<\/i> gene expression (0.25 vs. 0.55). However, COVID-19 patients with RAAS inhibitor (RAASi) intake had significantly shorter hospitalization times (5 vs. 12 days), higher viral loads (57,517 vs. 15,980\/10<sup>6<\/sup> RNase P-gene copies) and decreased <i>ACE\/ACE2<\/i>-expression ratios (4.58 vs. 11.07) than patients without. <i>TMPRSS2<\/i> expression was significantly (1.76-fold) higher in COVID-19 patients than controls. <b><i>Conclusion:<\/i><\/b> Our study delineates the heterogeneous expression patterns of RAAS components in the lungs, which vary amongst cellular populations, and implies that COVID-19 patients with RAASi-intake present with a more rapid disease progression, although this requires further investigation. <\/jats:p>","DOI":"10.1159\/000520221","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T22:00:31Z","timestamp":1639692031000},"page":"166-177","source":"Crossref","is-referenced-by-count":5,"title":["Immunohistochemical and Transcriptional Analysis of SARS-CoV-2 Entry Factors and Renin-Angiotensin-Aldosterone System Components in Lethal COVID-19"],"prefix":"10.1159","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7609-8612","authenticated-orcid":false,"given":"Jasmin Dionne","family":"Haslbauer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Stalder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Zinner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1729-1425","authenticated-orcid":false,"given":"Stefano","family":"Bassetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3074-6925","authenticated-orcid":false,"given":"Kirsten 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