Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB

Abstract

Purpose of Review Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the aggressive coronavirus disease pandemic. Recently, investigators have stipulated that COVID-19 patients receiving angiotensin-converting-enzyme inhibitors (ACEI) may be subject to poorer outcomes. This editorial presents the available evidence to guide treatment practices during this pandemic. Recent Findings Recent studies from Wuhan cohorts provide valuable information about COVID-19. A cohort with 52 critically ill patients revealed cardiac injury in 12% of patients. Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells. Investigators suspect that SARS-CoV-2 uses the ACE2 receptor to enter the lungs in a mechanism similar to SARS-CoV. Several hypotheses have been proposed to date regarding the net effect of ACEI/ARB on COVID-19 infections. Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB. Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated. Summary Even though physiological models of SARS-CoV infection show a theoretical benefit of ACEI/ARB, these findings cannot be extrapolated to SARS-CoV-2 causing COVID-19. Major cardiology scientific associations, including ACC, HFSA, AHA, and ESC Hypertension Council, have rejected these correlation hypotheses. After an extensive literature review, we conclude that there is no significant evidence to support an association for now, but given the rapid evolvement of this pandemic, findings may change.

A systematic review and meta-analysis to evaluate the clinical outcomes in COVID -19 patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers

“…Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB, suggesting the use of ACEI might be protective against respiratory complications. Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated, which may lead to severe pneumonia increasing risk of severe outcomes and mortality [32]. Individuals with ACE2 polymorphisms have an increased genetic predisposition for an increased risk of SARS-CoV-2 infection and may have harmful effects of ACEI/ARB [33].…”

Early prediction for severe COVID-19 with hypertension and intervention

“…Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are the rstline drugs widely used in patients with hypertension [14]. However, whether to continue to use ACEI/ARB in the setting of COVID-19 has caused widespread controversy [10,11].The continuous management of ACEI/ARB may prevent excessive activation of RAS by preventing ACE2 down-regulation, which is bene cial to reduce the risk of ARDS [7,15]. In addition, most hypertension itself has high RAS activity.Both hypertension and pharmacological RAS inhibition will increase ACE2 levels, which may increase human susceptibility and theoretically promote SARS-CoV-2 invasion and infection proliferation [10,11].The downregulation of ACE2 after SARS-CoV-2 infection will accelerate the destruction of RAS axis balance.Excessive accumulation of angiotensin II,and ADH will increase retention of water and sodium and decrease OP, which will conversely increase hypertension and further promote the progress of ARDS.This may be why COVID-19 patients with hypertension is more likely to increase severity.In theory, these patients should choose RAS inhibitors.…”

“…At present, in addition to traditional RAS inhibitors [7,15,16], some new drugs targeting the RAS axis have appeared. Recombinant human ACE2 (rhACE2) protein may play an important role in protecting ARDS patients [17],and has achieved good therapeutic effects in animal models and has entered clinical trials [18,19].The latest research data shows that recombinant human soluble (hrsACE2) can directly inhibit SARS-CoV-2 infection in engineered human blood vessel organoids and human kidney organoids, blocking the early stage of infection [20].In theory, systemic administration of hrsACE2 can neutralize SARS-CoV-2 and avoid the damage of alveolar epithelial cells caused by direct virus invasion, which has signi cant clinical application value.…”

Putative contributions of circadian clock and sleep in the context of SARS-CoV-2 infection

“…Furthermore, since ACE2, which may be regulated by clock activity, was shown to have a protective effect through suppression of apoptosis of pulmonary endothelial cells, it is possible that chronobiological interventions may mitigate the progression of lung injury, if such interventions occur in a very early stage of the infection (49). Alternatively, in light of clinical studies showing the relevance of chronoadequacy of ACE inhibitor therapy on hypertension(50), it is possible that administration of such agents in the context of SARS-Cov-2 infection may require more precise alignment with the patient circadian clock status (51), even though the evidence supporting such pharmacological treatment is doubtful at best(52).…”