ACE Inhibitors, ARBs and Other Anti-Hypertensive Drugs and Novel COVID-19: An Association Study from the COVID Symptom Tracker App in 2,215,386 Individuals

Background: Early pandemic data suggests that COVID-19 is more common in individuals with hypertension. SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). We aimed to identify whether RAAS inhibitors commonly used to treat hypertension alter risk of COVID-19 using self-reported data collected from 2,215,386 individuals completing the COVID Symptom Tracker App. Methods: Multivariate logistic regression models adjusted for age, body mass index and sex. Main outcome measures included self-reported COVID-19 infection with classical symptoms (SR-COVID19), self-reported positive COVID-19 test results (T-COVID19), and imputed COVID-19 based on symptomatology (I-COVID19). Findings: ACE inhibitor users had increased odds of SR-COVID19 (OR 1.95, 95% CI 1.89 - 2.03) especially when reporting breathlessness (OR 2.70, 95% CI 2.34 - 3.12). No increased odds were seen for T-COVID19 in a small tested subset (18,321). Models were similar in ACE inhibitor/angiotensin receptor blocker groups and robust to adjustment for heart disease and diabetes. Other antihypertensive classes showed reduced odds for SD-COVID19 (OR 0.53, 95% CI 0.48 - 0.58). Interpretation: RAAS inhibitors may modestly increase risk of symptomatic infection with COVID-19 in community populations, although causality is not established here. Other antihypertensives are associated with reduced presentation levels. Benefits and direct/inadvertent hazards of switching medications need to be carefully evaluated. Funding: Zoe Global Limited developed the COVID Symptom Tracker App pro bono for non-commercial purposes. Investigators received support from the Wellcome Trust, the MRC/BHF, EU, CDRF, and the NIHR-funded BioResource, Clinical Research Facility and BRC based at GSTT NHS Foundation Trust in partnership with KCL.