Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19)

Abstract

IMPORTANCEThe role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. OBJECTIVE To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. EXPOSURES History of taking ACEIs or ARBs at the time of COVID-19 testing. MAIN OUTCOMES AND MEASURES Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive.RESULTS A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). CONCLUSIONS AND RELEVANCEThis study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.

Association of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) with risk of mortality, severity or SARS-CoV-2 test positivity in COVID-19 patients: A systematic review and meta-analysis

“…In total, 10 studies comprising of 49,188 patients were included in this analysis. Of these, 4,274 SARS-CoV-2 positive patients were taking ACEIs/ARBs whereas 8,714 positive patients were non users of ACEIs/ARBs 1,[19][20][21][22][23][24][25][26][27] . Of these, eight studies provided data on mortality outcome, seven studies provided data on composite severe clinical manifestations outcome and only two studies provided data on SARS-CoV-2 test positivity as shown in Table 1.…”

“…Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to huge morbidity and mortality throughout the world since it was rst detected in early December of 2019 in Wuhan, China 1 . It has already been established that the SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptor of extracellular domain of the transmembrane to gain entry into the host cells 1,2 .…”

“…Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to huge morbidity and mortality throughout the world since it was rst detected in early December of 2019 in Wuhan, China 1 . It has already been established that the SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptor of extracellular domain of the transmembrane to gain entry into the host cells 1,2 . Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are frontline therapies in treating cardiovascular disorders including hypertension and diabetes, however, they may upregulate ACE2 expression in some animal models 1,3,4 .…”

“…It has already been established that the SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptor of extracellular domain of the transmembrane to gain entry into the host cells 1,2 . Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are frontline therapies in treating cardiovascular disorders including hypertension and diabetes, however, they may upregulate ACE2 expression in some animal models 1,3,4 . But data are limited for human studies showing variations on plasma ACE2 levels, most importantly no study had identi ed on their effect on lung-speci c expression of ACE2 1,5 .…”

“…deaths 6,7 . This may lead to clinical concerns that patients who are taking ACEIs/ARBs for combating cardiovascular diseases along with hypertension and diabetes are at an increased risk for becoming infected with SARS-CoV-2 and were being at the highest risk of worst clinical outcomes 1,8 . However, in this clinical debating situations, it has also been postulated that the ACE2 upregulation may improve clinical outcomes in SARS-CoV-2 infected patients by protecting lung injury 9 .…”