Association Between Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19 Infection in South Korea

Abstract

The severe acute respiratory syndrome coronavirus 2 is known to infect host cells by interacting with ACE2 (angiotensin-converting enzyme 2) expressed in the respiratory epithelium. There have been concerns on whether alterations of ACE2 expression by renin-angiotensin-aldosterone system (RAAS) inhibitors would contribute to the infectivity and severity of coronavirus disease 2019 (COVID-19). We performed a case-control study to investigate the association between RAAS inhibitors and risk and severity of COVID-19 infection in South Korea using the population-based data provided by the Korean National Health Insurance System. Of 16 281 subjects with hypertension, there were 950 (5.8%) confirmed COVID-19 cases. After case-control matching, multivariable-adjusted conditional logistic regression analysis was performed. The adjusted odds ratio and 95% CIs for COVID-19 infection and long-term hospitalization comparing exposure to RAAS inhibitors and nonexposure to RAAS inhibitors was 1.161 (0.958-1.407) and 0.863 (0.533-1.397), respectively. When comparing exposure to RAAS inhibitors and nonexposure to RAAS inhibitors for intensive care unit admission, high-flow oxygen therapy, and death, the adjusted odds ratios (95% CIs) were 1.515 (0.402-5.701), 0.663 (0.272-1.619), and 1.363 (0.513-3.662), respectively. In all analyses, P values were not significant (P>0.05). The present study demonstrates the absence of an identifiable association between the exposure to RAAS inhibitors and risk and severity of COVID-19 infection, supporting the current medical guidelines and recommendations that patients should not discontinue RAAS inhibitors out of a concern that they are at increased risk for infection or severe illness of COVID-19.

Keywords: COVID-19; Republic of Korea; antihypertensive agents; hypertension; renin-angiotensin system.