Excerpt

The coronavirus pandemic is mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been responsible for more than 900,000 infections and 45,000 deaths worldwide as of April 1, 2020 [1, 2]. The molecular mechanisms leading to SARS-CoV‑2 infection were identified at an incredible pace: Similar to SARS-CoV‑1, the virus which led to the SARS epidemic during 2002–2004, SARS-CoV‑2 infects cells via binding to angiotensin-converting enzyme 2 (ACE2; [3]). Therefore, concerns were raised that higher expression of ACE2 in the respiratory tract may expedite the infection. However, ACE2 also plays beneficial roles in the renin–angiotensin–aldosterone system (RAAS) where it metabolizes angiotensin II (Ang-2), a vasoconstrictor, to angiotensin-(1–7) (Ang-(1–7)), a vasodilator with antihypertrophic properties. Thus, consumption of ACE2 by the virus may result in an overshooting activation of the RAAS. Importantly, inhibitors of angiotensin-converting enzyme inhibitors (ACEI) as well as AT₁-receptor blockers (ARB) have been shown in experimental studies to upregulate ACE2 and ACE levels in various tissues [4, 5]. Both ACEI and ARB are widely used for the treatment of heart failure and hypertension, especially in patients with diabetes. The observation that patients suffering from these conditions are at increased risk of dying from SARS-CoV‑2 infection [S1] raised reasonable concerns about whether these drugs might increase the risk of both SARS-CoV‑2 infection and an unfavorable course of the disease. However, several important issues regarding the involvement of ACE2 in the disease and the interaction of its expression and activity with the administration of RAAS-modulating drugs are not fully understood yet: …