Why angiotensin II is a poor choice for circulatory support of ventilated COVID-19 patients compared to vasopressin

Early in the COVID-19 pandemic when it was first reported that SARS-CoV-2 used membrane-bound angiotensin-converting enzyme-2 (ACE2) as its receptor for entry into cells, warnings were raised against the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) because of their potential to increase ACE2 expression. These reports ignored the adverse effects that the renin-angiotensin system (RAS) exerts on the cardiovascular system and kidneys via its primary hormone angiotensin (Ang) II acting upon AT1 receptors that could exacerbate the cytokine storm induced by SARS-CoV-2 [1]. At one point it was even recommended that COVID-19 patients suffering from cardiovascular collapse be administered Ang II to restore blood pressure rather than norepinephrine or vasopressin [2]. An alternative strategy for treating COVID-19 was the administration of soluble ACE2 (sACE2) to act as a decoy receptor for the virus, misdirecting it away from vulnerable cells expressing membrane bound ACE2 [3-5]. However, a paper published in early 2021 [6] described a scenario in which sACE2 and vasopressin played essential roles in SARS-CoV-2 infection of cells vulnerable to the virus. This commentary challenges both the [2] and [6] reports based upon their misconceptions and technical errors that pose a threat to the administration of life-saving therapies for severely affected COVID-19 patients.