Renin-angiotensin system inhibitor discontinuation in COVID-19 did not modify systemic ACE2 in a randomized controlled trial

Vincent Rathkolb; Marianna T Traugott; Andreas Heinzel; Marko Poglitsch; Judith Aberle; Farsad Eskandary; Agnes Abrahamowicz; Martin Mueller; Petra Knollmueller; Tarik Shoumariyeh; Jasmin Stuflesser; Ivan Seeber; Georg Gibas; Hannah Mayfurth; Viktoria Tinhof; Lukas Schmoelz; Markus Zeitlinger; Christian Schoergenhofer; Bernd Jilma; Bernd Genser; Wolfgang Hoepler; Sara Omid; Mario Karolyi; Christoph Wenisch; Rainer Oberbauer; Alexander Zoufaly; Manfred Hecking; Roman Reindl-Schwaighofer

doi:10.1016/j.isci.2023.108146

Renin-angiotensin system inhibitor discontinuation in COVID-19 did not modify systemic ACE2 in a randomized controlled trial

iScience. 2023 Oct 5;26(11):108146. doi: 10.1016/j.isci.2023.108146. eCollection 2023 Nov 17.

Authors

Vincent Rathkolb¹, Marianna T Traugott², Andreas Heinzel¹, Marko Poglitsch³, Judith Aberle⁴, Farsad Eskandary¹, Agnes Abrahamowicz¹, Martin Mueller⁵, Petra Knollmueller⁵, Tarik Shoumariyeh¹, Jasmin Stuflesser², Ivan Seeber², Georg Gibas², Hannah Mayfurth¹, Viktoria Tinhof¹, Lukas Schmoelz¹, Markus Zeitlinger⁵, Christian Schoergenhofer⁵, Bernd Jilma⁵, Bernd Genser⁶, Wolfgang Hoepler², Sara Omid², Mario Karolyi², Christoph Wenisch², Rainer Oberbauer¹, Alexander Zoufaly^{2

7}, Manfred Hecking¹, Roman Reindl-Schwaighofer¹

Affiliations

¹ Department of Internal Medicine III, Clinical Division of Nephrology & Dialysis, Medical University of Vienna, Wien, Austria.
² Department of Internal Medicine IV with Infectious Diseases and Tropical Medicine, Clinic Favoriten, Vienna, Austria.
³ Attoquant Diagnostics, Vienna, Austria.
⁴ Institute of Virology, Medical University of Vienna, Wien, Austria.
⁵ Department of Clinical Pharmacology, Medical University of Vienna, Wien, Austria.
⁶ Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
⁷ Faculty of Medicine, Sigmund Freud University, Vienna, Austria.

Abstract

Despite the similar clinical outcomes after renin-angiotensin system (RAS) inhibitor (RASi) continuation or withdrawal in COVID-19, the effects on angiotensin-converting enzyme 2 (ACE2) and RAS metabolites remain unclear. In a substudy of the randomized controlled Austrian Corona Virus Adaptive Clinical Trial (ACOVACT), patients with hypertension and COVID-19 were randomized 1:1 to either RASi continuation (n = 30) or switch to a non-RASi medication (n = 29). RAS metabolites were analyzed using a mixed linear regression model (n = 30). Time to a sustained clinical improvement was equal and ACE2 did not differ between the groups but increased over time in both. Overall ACE2 was higher with severe COVID-19. ACE-S and Ang II levels increased as expected with ACE inhibitor discontinuation. These data support the safety of RASi continuation in COVID-19, although RASi were frequently discontinued in our post hoc analysis. The study was not powered to draw definite conclusions on clinical outcomes using small sample sizes.

Keywords: Human metabolism; Virology.