1. No association was found between angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use and test-positivity for COVID-19.
Evidence Rating Level: 2 (Good)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), gains entry into host cells by binding to the extracellular domain of transmembrane angiotensin-converting enzyme 2 (ACE2) receptors. Given the limited human data on ACE2 expression in the lungs, knowing that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) upregulate ACE2 expression in animals does not provide sufficient information regarding their safety in COVID-19 patients. This retrospective cohort study as part of a prospective, observational study of all individuals tested for COVID-19 within the Cleveland Clinic Health System sought to determine the associations of ACEi and ARB use with the risk of incident SARS-CoV-2. to . Participants were tested for COVID-19 between March 8, 2020 and April 12, 2020 through nasopharyngeal and oropharyngeal swabs. A total of 18,472 patients (M [SD] age = 49  years, 60% female, 69% Caucasian) were tested and subsequently included in analysis. Approximately 9.4% were COVID-19-positive. Among them, 9.3% were admitted to the ICU, 24.3% were admitted to the hospital, and 6.4% required mechanical ventilation. A high prevalence of comorbidities was noted in this COVID-19-positive group: hypertension (40%), diabetes (19%), coronary artery disease (12%), chronic obstructive pulmonary disease (12%), and heart failure (10%). A total of 116 (6.7%) of test-positive patients were taking ACEis and 98 (5.6%) were taking ARBs, which represented a group with a greater number of comorbidities than those who were not taking these medications. In those taking ACEIis, the test positivity rates were 8.6% and 9.5% in patients not taking ACEis (overlap propensity score-weighted OR 0.89, 95% CI 0.72 to 1.10). Those taking ARBs had a test positivity rate of 10.0% while this rate was 9.3% in those not taking ARBs (overlap propensity score-weighted OR 1.09, 95% CI 0.87 to 1.37). A total of 54% of patients taking ACEis were admitted to the hospital compared to 39% not taking these medications (OR 1.84, 95% CI 1.22 to 2.79), 24% of ACEi users were admitted to an ICU (OR 1.77, 95% CI 1.07 to 2.92), and 14% required mechanical ventilation (OR 1.35, 95% CI 0.74 to 2.47). In terms of ARB use in positive patients, 53% were admitted to the hospital (OR 1.61, 95% CI 1.04 to 2.50), 20% were admitted to an ICU (OR 1.16, 95% CI 0.67 to 2.02), and 14% required mechanical ventilation (OR 1.12, 95% CI 0.59 to 2.12). A total of 42 deaths occurred among 1,705 patients with available death data, with 3.8% taking either ACEis or ARBs and 2.1% not taking either medication type. This may be a representation of the effect of underlying comorbidities rather than medication effect. Overall, this study found no associations between ACEi or ARB use and risk of COVID-19, but the results cannot be used for conclusive evidence regarding outcomes.
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