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A low aldosterone/renin ratio and high soluble ACE2 associate with COVID-19 severity.

  • Akin, Sakir1, 2
  • Schriek, Paula3
  • van Nieuwkoop, Cees4
  • Neuman, Rugina I5
  • Meynaar, Iwan1
  • van Helden, Erik J4
  • Bouazzaoui, Hassan El3
  • Baak, Remon1
  • Veuger, Marjan6
  • Mairuhu, Ronne A T A4
  • van den Berg, Lettie1
  • van Driel, Vincent7
  • Visser, Loes E8
  • de Jonge, Evert9
  • Garrelds, Ingrid M5
  • Duynstee, Johannes F A B10
  • van Rooden, Jan Kees11
  • Ludikhuize, Jeroen1
  • Verdonk, Koen5
  • Caliskan, Kadir2
  • And 3 more
  • 1 Department of Intensive Care, Haga Teaching Hospital, The Hague, The Netherlands. , (Netherlands)
  • 2 Department of Cardiology, Unit Heart Failure and Transplant Unit, Erasmus MC University Medical Center, Rotterdam.
  • 3 Department of Pulmonology.
  • 4 Department of Internal Medicine, Haga Teaching Hospital, The Hague.
  • 5 Department of Internal Medicine, Division of Vascular Medicine and Pharmacology Erasmus MC University Medical Center, Rotterdam.
  • 6 Department of Clinical Chemistry.
  • 7 Department of Cardiology.
  • 8 Department of Hospital Pharmacy, Haga Teaching Hospital, The Hague.
  • 9 Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam.
  • 10 Department of Haga Science.
  • 11 Department of Radiology, Haga Teaching Hospital, The Hague, The Netherlands. , (Netherlands)
Published Article
Journal of hypertension
Publication Date
Mar 01, 2022
DOI: 10.1097/HJH.0000000000003054
PMID: 34862332


The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers have been suggested to upregulate ACE2, their use in COVID-19 patients is now considered well tolerated. The aim of our study was to investigate parameters that determine COVID-19 severity, focusing on RAAS-components and variation in the genes encoding for ACE2 and TMPRSS2. Adult patients hospitalized due to SARS-CoV-2 infection between May 2020 and October 2020 in the Haga Teaching Hospital were included, and soluble ACE2 (sACE2), renin, aldosterone (in heparin plasma) and polymorphisms in the ACE2 and TMPRSS2 genes (in DNA obtained from EDTA blood) were determined. Out of the 188 patients who were included, 60 were defined as severe COVID-19 (ICU and/or death). These patients more often used antidiabetic drugs, were older, had higher renin and sACE2 levels, lower aldosterone levels and a lower aldosterone/renin ratio. In addition, they displayed the TMPRSS2-rs2070788 AA genotype less frequently. No ACE2 polymorphism-related differences were observed. Multivariate regression analysis revealed independent significance for age, sACE2, the aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype as predictors of COVID-19 severity, together yielding a C-index of 0.79. Findings were independent of the use of RAAS blockers. High sACE2, a low aldosterone/renin ratio and having the TMPRSS2 rs2070788 non-AA genotype are novel independent determinants that may help to predict COVID-19 disease severity. retrospectively registered. Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

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