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Review
. 2020 Jul;43(7):648-654.
doi: 10.1038/s41440-020-0455-8. Epub 2020 Apr 27.

Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19

Hisashi Kai  1 , Mamiko Kai  2
Affiliations
Review

Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19

Hisashi Kai et al. Hypertens Res. 2020 Jul.

Abstract

The rapid spread of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19). Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19. On the other hand, animal data suggested a potential protective effect of ARBs against COVID-19 pneumonia because an ARB prevented the aggravation of acute lung injury in mice infected with SARS-CoV, which is closely related to SARS-CoV-2. Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.

Keywords: Acute lung injury; Angiotensin II type-1 receptor; Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitor; Severe acute respiratory syndrome coronavirus 2.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Possible scheme of the association of ACE2, angiotensin II, and AT1R and acute lung injury of SARS and COVID-19. Ang II, angiotensin II; ACE, angiotensin-converting enzyme; ACE2, angiotensin-converting enzyme 2; ACEI, angiotensin-converting enzyme inhibitor; AT1R, angiotensin II type-1 receptor; ARB, angiotensin II type-1 receptor blocker; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; S-protein, spike-glycoprotein
Fig. 2
Fig. 2
SARS-CoV spike mediates lung injury through modulation of angiotensin II in acid aspiration mice. a Lung angiotensin II levels in SARS-CoV-S protein (spike-Fc protein)- or control Fc protein-treated mice after acid or saline aspiration. *P < 0.05 vs. control-treated mice after acid aspiration. b Effects of losartan (15 mg/kg) (AT1 inhibitor) on lung elastance measurements in acid plus spike-Fc protein-treated mice (n = 4–6 per group). P < 0.05 comparing losartan-treated spike-Fc–challenged mice with vehicle-treated spike-Fc–challenged mice. c Effects of losartan (15 mg/kg) on lung edema (wet/dry weight ratio) in acid plus spike-Fc protein-treated mice (n = 4–6 per group). P < 0.05 vs. vehicle-treated wild-type mice after acid injury. AT1, angiotensin II type-1 receptor. Cited from ref. [27]
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