TY - JOUR T1 - Increased blood Angiotensin Converting Enzyme 2 activity in critically ill COVID-19 patients JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00848-2020 SP - 00848-2020 AU - Dirk van Lier AU - Matthijs Kox AU - Karine Santos AU - Hans van der Hoeven AU - Janesh Pillay AU - Peter Pickkers Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2021/01/21/23120541.00848-2020.abstract N2 - Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers (ARBs) are cornerstone treatments in several cardiovascular disease entities [1]. The RAAS is a central regulator of blood pressure, consisting of two counterregulatory pathways, commonly described as classical and non-classical, respectively [1]. The main effect of classical RAAS activation is the generation of angiotensin II by angiotensin converting enzyme (ACE) [1]. In contrast, non-classical RAAS activation results in cleavage of angiotensin II by angiotensin converting enzyme-2 (ACE2) to form angiotensin 1–7, which directly counteracts the effects of classical RAAS activation [1].As early as March 2020, observational studies reported associations between hypertension and Coronavirus-19 (COVID-19) disease outcome [2]. Concerns about the risk of ACE-inhibitors and ARBs were quickly raised, as these drugs were implied to upregulate ACE2, the functional receptor for SARS-coronavirus 2 (SARS-CoV-2), thereby putatively increasing SARS-CoV-2 virulence [2]. However, a recent large observational study mitigated these concerns by demonstrating neither increased susceptibility for COVID-19, nor impaired outcome of COVID-19 patients on ACE-inhibitor/ARB therapy [3]. Other observational data even suggest improved outcome of COVID-19 patients on ACE-inhibitor/ARB therapy [4], a finding currently being investigated in a randomised controlled trial (ClinicalTrials.gov NCT04311177).Although observational studies highlight ACE2 as both friend and foe in COVID-19, there is a paucity of actual data on angiotensin metabolism in COVID-19. This is highly warranted to determine a possible causative relationship between ACE2 and COVID-19 severity.The study was carried out in the Netherlands in accordance with the applicable rules concerning the review of research ethics committees and informed consent. All patients or legal representatives were informed about the study details and could decline … ER -