Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety

<p dir="ltr">The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. These comorbidities have adverse outcomes in COVID-19 patients that might result from pharmacotherapy. Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1–7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes- and/or hypertension-induced end-organ damage. Thus, there existed clinical uncertainty. Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels <i>in vivo</i> and the available literature on the clinical safety of these drugs in COVID-19 patients. Further, in a re-analysis of clinical data from a meta-analysis of 9 studies, we show that ACEIs/ARBs usage was not associated with an increased risk of all-cause mortality. Literature suggests that ACEIs/ARBs usage generally appears to be clinically safe though their use in severe COVID-19 patients might increase the risk of acute renal injury. For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Drug Targeting<br>License: <a href="http://creativecommons.org/licenses/by-nc-nd/4.0/" target="_blank">http://creativecommons.org/licenses/by-nc-nd/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1080/1061186x.2020.1797754" target="_blank">https://dx.doi.org/10.1080/1061186x.2020.1797754</a></p>