Severe acute respiratory syndrome coronavirus 2 and renin-angiotensin system blockers: A review and pooled analysis

Mathieu Kerneis, Arnaud Ferrante, Paul Guedeney, Eric Vicaut, Gilles Montalescot

A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing an international outbreak of respiratory illness described as coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects human cells by binding to angiotensin-converting enzyme 2. Small studies suggest that renin-angiotensin system (RAS) blockers may upregulate the expression of angiotensin-converting enzyme 2, affecting susceptibility to SARS-CoV-2. This may be of great importance considering the large number of patients worldwide who are treated with RAS blockers, and the well-proven clinical benefit of these treatments in several cardiovascular conditions. In contrast, RAS blockers have also been associated with better outcomes in pneumonia models, and may be beneficial in COVID-19. This review sought to analyse the evidence regarding RAS blockers in the context of COVID-19 and to perform a pooled analysis of the published observational studies to guide clinical decision making. A total of 21 studies were included, comprising 11,539 patients, of whom 3417 (29.6%) were treated with RAS blockers. All-cause mortality occurred in 587/3417 (17.1%) patients with RAS blocker treatment and in 982/8122 (12.1%) patients without RAS blocker treatment (odds ratio 1.00, 95% confidence interval 0.69–1.45; P=0.49; I2=84%). As several hypotheses can be drawn from experimental analysis, we also present the ongoing randomized studies assessing the efficacy and safety of RAS blockers in patients with COVID-19. In conclusion, according to the current data and the results of the pooled analysis, there is no evidence supporting any harmful effect of RAS blockers on the course of patients with COVID-19, and it seems reasonable to recommend their continuation.

RAS blockers, COVID-19

• ACE: Angiotensin-Converting Enzyme
• ACE-I: Angiotensin-Converting Enzyme Inhibitors
• ARBs: Angiotensin II Receptor Blockers
• AT1/AT2 receptor: Angiotensin II type 1/2 receptor
• CI: Confidence Interval
• COVID-19: Coronavirus Disease 2019
• mRNA: messenger Ribonucleic Acid
• RAS: Renin-Angiotensin System
• RNA: Ribonucleic Acid
• SARS: Severe Acute Respiratory Syndrome
• SARS-CoV: Severe Acute Respiratory Syndrome Coronavirus
• SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2

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