ACE-Inhibitors, Angiotensin Receptor Blockers and Endothelial Injury in COVID-19.

BACKGROUND COVID-19 is caused by the coronavirus SARS-CoV-2, which uses Angiotensin Converting Enzyme-2 (ACE-2) as a receptor for cellular entry. It is theorized that ACE-inhibitors (ACE-Is) or Angiotensin Receptor Blockers (ARBs) may increase vulnerability to SARS-CoV-2 by up-regulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration. OBJECTIVE To determine whether ACE-I and ARB use is associated with Acute Kidney Injury (AKI), macrovascular thrombosis, and in-hospital mortality. METHODS A retrospective, single-center study of 558 hospital inpatients with confirmed COVID-19 admitted from 1st  March - 30th  April 2020, followed up until 24th May 2020. AKI and macrovascular thrombosis were primary endpoints, in-hospital mortality was a secondary endpoint. RESULTS AKI occurred in 126 (23.1%) patients, 34 (6.1%) developed macrovascular thrombi, 200 (35.9%) died. Overlap propensity score weighted analysis showed no significant effect of ACE-I/ARB use on the risk of occurrence of the specified endpoints. On exploratory analysis, severe Chronic Kidney Disease (CKD) increases odds of macrovascular thrombi (OR 8.237, 95% CI 1.689-40.181, p=0.009). The risk of AKI increased with advancing age (OR 1.028, 95% CI 1.011-1.044, p=0.001) and diabetes (OR 1.675, 95% CI 1.065-2.633, p=0.025). Immunosuppression was associated with lower risk of AKI (OR 0.160, 95%CI 0.029-0.886, p=0.036). Advancing age, dependence on care, male gender and eGFR <60ml/min/1.73m2 increased odds of in-hospital mortality. CONCLUSION We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi, or mortality. This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic.