tetano
Editor, Senior Moderator
Pathobiology
. 2021 Dec 16;1-12.
doi: 10.1159/000520221. Online ahead of print.
Immunohistochemical and Transcriptional Analysis of SARS-CoV-2 Entry Factors and Renin-Angiotensin-Aldosterone System Components in Lethal COVID-19
Jasmin Dionne Haslbauer[SUP] 1 [/SUP], Anna Stalder[SUP] 1 [/SUP], Carl Zinner[SUP] 2 [/SUP], Stefano Bassetti[SUP] 3 [/SUP], Kirsten Diana Mertz[SUP] 4 [/SUP], Philip Went[SUP] 5 [/SUP], Matthias Matter[SUP] 1 [/SUP], Alexandar Tzankov[SUP] 1 [/SUP]
Affiliations
Abstract
Introduction: 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.
Methods: Lung tissue from COVID-19 autopsies (n = 27) and controls (n = 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, in-situ hybridization and quantitative reverse transcriptase polymerase chain reaction. Gene expression profiling for ACE2, ACE and TMPRSS2 was performed.
Results: 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 ACE2 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. 15,980/106 RNase P-gene copies) and decreased ACE/ACE2-expression ratios (4.58 vs. 11.07) than patients without. TMPRSS2 expression was significantly (1.76-fold) higher in COVID-19 patients than controls.
Conclusion: 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.
Keywords: Angiotensin converting enzyme-2; Coronavirus disease 2019; Renin-angiotensin-aldosterone system; Severe acute respiratory syndrome coronavirus-2; Transmembrane protease serine subtype-2.
. 2021 Dec 16;1-12.
doi: 10.1159/000520221. Online ahead of print.
Immunohistochemical and Transcriptional Analysis of SARS-CoV-2 Entry Factors and Renin-Angiotensin-Aldosterone System Components in Lethal COVID-19
Jasmin Dionne Haslbauer[SUP] 1 [/SUP], Anna Stalder[SUP] 1 [/SUP], Carl Zinner[SUP] 2 [/SUP], Stefano Bassetti[SUP] 3 [/SUP], Kirsten Diana Mertz[SUP] 4 [/SUP], Philip Went[SUP] 5 [/SUP], Matthias Matter[SUP] 1 [/SUP], Alexandar Tzankov[SUP] 1 [/SUP]
Affiliations
- PMID: 34915500
- DOI: 10.1159/000520221
Abstract
Introduction: 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.
Methods: Lung tissue from COVID-19 autopsies (n = 27) and controls (n = 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, in-situ hybridization and quantitative reverse transcriptase polymerase chain reaction. Gene expression profiling for ACE2, ACE and TMPRSS2 was performed.
Results: 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 ACE2 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. 15,980/106 RNase P-gene copies) and decreased ACE/ACE2-expression ratios (4.58 vs. 11.07) than patients without. TMPRSS2 expression was significantly (1.76-fold) higher in COVID-19 patients than controls.
Conclusion: 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.
Keywords: Angiotensin converting enzyme-2; Coronavirus disease 2019; Renin-angiotensin-aldosterone system; Severe acute respiratory syndrome coronavirus-2; Transmembrane protease serine subtype-2.