Anti-hypertensive drugs possibly affect COVID-19 outcome through the double-edged sword ACE2*

J.A. Offerhaus, C.R. Bezzina

Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam UMC, Location Academic Medical Center, Amsterdam, The Netherlands

*Weergave van bespreking tijdens Journal Club meeting van de afdelingen cardiologie van Amsterdam UMC en OLVG d.d. 25 maart 2020

Discussion is ongoing whether specific anti-hypertensive drugs (AHD), like ACE-inhibitors (ACE-i) and Angiotensin Receptor Blockers (ARBs), can affect the outcome of a COVID-19 infection.

Such an effect is hypothesized to occur through the membrane protein, Angiotensin Converting Enzyme 2 (ACE2), which functions as the receptor through which SARS-COV-2 infects the cell.1

ACE2 is expressed in various tissues, including the heart.2 Preclinical studies have suggested that the expression of ACE2 is increased by AHD.3

In this respect, AHD may increase the risk of a SARS-COV-2 infection. On the other hand, other preclinical studies conducted on SARS-COV-1 (which also uses ACE2 for cell entry) have shown that upon infection, the level of ACE2 in the cell decreases.

ACE2 converts Ang2 into Ang1-7 and has thereby been considered an interesting target for treating cardiovascular disease.4

Thus, a decrease in ACE2 is expected to be detrimental, at least in part due to accumulation of Ang2.5

In this respect, an increase in ACE2 by AHD can counteract the potential negative effects of Ang2.6

A first retrospective study seems to indicate a (small) beneficial effect of ACE-i/ARBs usage.7


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