Effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the angiotensin-converting enzyme 2 levels in experimental models, and clinical outcomes of COVID-19 in humans

• Main Authors: Gábor Kriszta, Zsófia Kriszta, Bálint Erőss, Gabriella Pár, Péter Jenő Hegyi, Szilárd Váncsa, Szabolcs Kiss, Katalin Márta, Levente Frim, Lóránd Kiss, Margit Solymár, Gábor Pethő, László Czopf, Zsolt Szakács, Péter Hegyi, Erika Pintér
• Format: Other/Unknown Material
• Language: unknown
• Published: Zenodo 2020
• Subjects: COVID-19; severity; SARS-CoV-2; pandemic; coronavirus; angiotensin receptor blocker; angiotensin-converting enzyme inhibitor; angiotensin-converting enzyme-2; animal models; Antarc*; Antarctica
• Online Access: https://doi.org/10.5281/zenodo.3763384

Introduction A new coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), was first reported to cause human infection in Wuhan, China, in December 2019. The virus by now has been detected in all continents except Antarctica. The name represents the form of “corona,” from the many crown-like spike proteins on the surface of the virus. These spikes thought to be the main domain in connection to angiotensin-converting enzyme 2 (ACE2) on the cell surface; therefore, the mechanism of virus entry is already hypothesized. There are disagreements about the use of the renin-angiotensin-aldosterone system (RAAS) inhibitors that may alter ACE2 expression. Therefore, the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and the consequent dynamics in ACE2 expression might affect the virulence and the outcome of the infection. Coronavirus disease-19 (COVID-19) is a pandemic with significant mortality. One of the critical comorbidities leading to adverse outcomes is cardiovascular disease (CVD). Patients with cardiovascular diseases (CVDs) are often treated with ACEIs and ARBs acting on RAAS. ACEIs and ARBs might upregulate the expression of ACE2, providing more gates to the virus to enter the cells; they also exert beneficial hemodynamic, anti-inflammatory, and tissue-protective effects. Given the frequent use of ACEIs and ARBs worldwide, evidence-based recommendations on the use of these agents in patients with COVID-19 is urgently needed. Aim First, we aim to investigate the effects of ACEIs and ARBs on ACE2 activity and expression in experimental in vitro and in vivo animal models. Second, we will examine the impact of ACEIs and ARBs on the reported outcomes of COVID-19 involving patients’ data. Scientific questions in the systematic review on experimental data are: Whether the angiotensin-converting enzyme inhibitors and angiotensin receptor blockers could influence the expression of the ACE2? What is the tissue distribution of ACE2? What is the role ...