RE: Association between angiotensin blockade and COVID-19 severity in Hong Kong: a territory-wide study

We read this commentary(1) with interest on the role of angiotensin converting enzymes inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are in COVID-19 incidence and severity. Recent observational studies did not show increased risk of disease severity with ACEI/ARB use,(2,3) and an observational study(4) even reported a lower mortality risk with ACEIs (adjusted odds ratio [aOR]:0.33). However, all these studies did not adjust for laboratory parameters, which may confound the observed association.

We conducted a territory-wide retrospective cohort study by retrieving data from territory-wide electronic healthcare database ing Hong Kong Hospital Authority. We identified all patients aged ≥18 years diagnosed with COVID-19 between 1 January 2020 and 27 April 2020. The primary outcome was severe disease including (1)severe pneumonia, (2)critical complication (respiratory failure, septic shock and/or multiple organ dysfunction), (3)ventilatory support (invasive or non-invasive), (4)intensive care unit admission or (5)death. Drug exposure including ACEIs and ARBs was defined as ever exposure within 5 years before admission. Multivariable logistic regression model was performed by adjusting for other covariates including age, sex, comorbidities (diabetes mellitus, hypertension, ischemic heart disease, stroke and atrial fibrillation), other medications (aspirin, statins, proton pump inhibitors), and laboratory parameters (leukocyte, platelet, C-reactive protein [CRP], creatinine, sodium, potassium, alkaline phosphatase, alanine aminotransferase, albumin, globulin, and lactate dehydrogenase [LDH]).

Of 734 COVID-19 patients, 73 (9.9%) had severe disease as defined. There were 13 and 18 ACEI and ARB users. ACEI use was associated with a lower risk of severe disease (aOR:0.14, 95 % CI:0.02–0.87), but there was no significant association between ARB use and severe disease (aOR:1.86, 95% CI:0.31–9.97). Other independent risk factors for severe disease were leukocyte count >11x109/L (aOR:5.98, 95% CI:1.55–2.19), C-reactive protein >1mg/dL (aOR:3.42, 95% CI,:1.76–6.68), and lactate dehydrogenase >280U/L (aOR:5.91, 95% CI:2.89–12.13).

Our findings corroborate the results of Mehra et al,(4) which showed a lower mortality with ACEI use. While ACEI/ARBs should not be discontinued in COVID-19 patients, further multi-center studies including patients of different ethnicities are needed to clarify the potential beneficial effects of ACEIs.