Angiotensin II - A Brief Review and Role in Severe SARS-COV-2 Sepsis.

The renin-angiotensin-aldosterone system (RAAS), whose major vasopressor effector is angiotensin II (ATII), has multiple activities and regulates sodium-water homeostasis and fluid and blood pressure homeostasis. RAAS plays a crucial role in cardiocirculatory shock because it counteracts hypotension and hypovolemia by activating different physiologic responses. Based on the encouraging results of the ATHOS-3 trial, the US Food and Drug Administration and the European Medicines Agency approved the use of ATII for catecholamine-resistant vasodilatory shock. More recently, ATII was used for the compassionate treatment of critically ill patients with COVID-19. Beyond its vasopressor properties, ATII was hypothesized to have antiviral activity because it induces internalization and degradation of angiotensin-converting enzyme 2 receptors used by SARS-Cov-2 to infect cells. Overall, the use of ATII in patients with COVID-19 showed promising results because its administration was associated with the achievement and maintenance of target mean arterial pressure, increased PaO2/FIO2 ratio, and decreased FIO2. The aim of this narrative review is to summarize the available knowledge on the use of ATII in patients with COVID-19.

Angiotensin II Administration in Patients With COVID-19 Shock.

PURPOSE: To understand the hemodynamic effect of angiotensin II as a vasopressor in patients with shock secondary to COVID-19 infection. METHODS: A retrospective analysis was performed on all patients at a single center with COVID-19 infection and shock who were treated with angiotensin II. The hemodynamic response to angiotensin II was estimated by recording the mean arterial pressure, norepinephrine equivalent dose (NED) and urine output. RESULTS: Ten patients with COVID-19 related shock were treated with angiotensin II. Over the initial 6 hours, the average the NED decreased by 30.4% (from 64.6 to 44 µg/min) without a significant change in the mean arterial pressure (0.7% decrease). Six patients experienced at least a 25% reduction in NED by 6 hours, and 2 experienced at least a 50% reduction. CONCLUSIONS: On average, the hemodynamic response to angiotensin II in COVID-19 related shock was favorable. Two patients had a marked rapid improvement. Given the relationship of SARS-CoV-2 with the renin-angiotensin-aldosterone system, further evaluation of angiotensin II for the treatment of COVID-19 related shock is warranted.

From Angiotensin II to Cyclic Peptides and Angiotensin Receptor Blockers (ARBs): Perspectives of ARBs in COVID-19 Therapy.

The octapeptide hormone angiotensin II is one of the most studied peptides with the aim of designing and synthesizing non-peptide mimetics for oral administration. To achieve this, cyclizations at different positions within the peptide molecule has been a useful strategy to define the active conformation. These studies on angiotensin II led to the discovery of Sarmesin, a type II angiotensin II antagonist, and the breakthrough non-peptide mimetic Losartan, the first in a series of sartans marketed as a new generation of anti-hypertensive drugs in the 1990s. Angiotensin II receptor blockers (ARBS) and angiotensin I converting enzyme inhibitors (ACEI) were recently reported to protect hypertensive patients infected with SARS-CoV-2. The renin-angiotensin system (RAS) inhibitors reduce excess angiotensin II and increase antagonist heptapeptides alamandine and aspamandine which counterbalance angiotensin II and maintain homeostasis and vasodilation.

Effective Use of Angiotensin II in Coronavirus Disease 19-Associated Mixed Shock State: A Case Report.

The rapid spread of Coronavirus Disease 2019 (COVID-19) has sparked a search for effective therapies. The discovery that the virus binds the angiotensin-converting enzyme 2 (ACE2) receptor has led to investigation of the renin-angiotensin system for possible therapeutic targets. We present a case of an elderly woman with multiple comorbidities who developed severe acute respiratory distress syndrome (ARDS), a cardiomyopathy, and vasodilatory shock secondary to COVID-19 and was treated with exogenous angiotensin II. She rapidly demonstrated significant hemodynamic improvement without noted adverse effects. Thus, we propose further investigation into possible benefits of angiotensin II in shock secondary to COVID-19.