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

Sakir Akin, Paula Schriek, Cees van Nieuwkoop, Rugina I. Neuman, Iwan Meynaar, Erik J. van Helden, Hassan El Bouazzaoui, Remon Baak, Marjan Veuger, Ronne A.T.A. Mairuhu, Lettie van den Berg, Vincent van Driel, Loes E. Visser, Evert de Jonge, Ingrid M. Garrelds, Johannes F.A.B. Duynstee, Jan Kees van Rooden, Jeroen Ludikhuize, Koen Verdonk, Kadir CaliskanTim Jansen, Ron H.N. van Schaik, A. H.Jan Danser

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
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BACKGROUND: 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. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: retrospectively registered.

Original languageEnglish
Pages (from-to)606-614
Number of pages9
JournalJournal of Hypertension
Issue number3
Publication statusPublished - 1 Mar 2022

Bibliographical note

Funding Information:
We thank the Haga Science Department for their financial support.

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.


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