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Immunohistochemical and Transcriptional Analysis of SARS-CoV-2 Entry Factors and Renin-Angiotensin-Aldosterone System Components in Lethal COVID-19.
Haslbauer, Jasmin Dionne; Stalder, Anna; Zinner, Carl; Bassetti, Stefano; Mertz, Kirsten Diana; Went, Philip; Matter, Matthias; Tzankov, Alexandar.
  • Haslbauer JD; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Stalder A; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Zinner C; Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Bassetti S; Division of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Mertz KD; Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  • Went P; Institute of Pathology, Cantonal Hospital Graubünden, Chur, Switzerland.
  • Matter M; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Tzankov A; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Pathobiology ; 89(3): 166-177, 2022.
Article in English | MEDLINE | ID: covidwho-1574506
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Observational study Limits: Humans Language: English Journal: Pathobiology Journal subject: Pathology Year: 2022 Document Type: Article Affiliation country: 000520221

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Observational study Limits: Humans Language: English Journal: Pathobiology Journal subject: Pathology Year: 2022 Document Type: Article Affiliation country: 000520221