- This retrospective study followed 9,101 household contacts of patients who tested positive for COVID-19; among the contacts, 1,499 were taking an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at study entry
- After adjustment for age, gender, race/ethnicity, English proficiency, comorbid conditions and date of study entry, ACEI/ARB use was associated with a significantly decreased risk of a COVID-19 diagnosis (OR, 0.60; P=0.00)
- The results were similar when ACEI and ARB use were analyzed separately
- The strength of the association between ACEI/ARB use and decreased COVID-19 risk was similar in all subgroups studied, and no other medication classes were associated with reduced risk of COVID-19
- These findings support the current professional recommendations that use of ACEIs and ARBs should not be discontinued because of concern about COVID-19
The claim that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) might increase the risk of COVID-19 is a subject of keen interest and controversy. Animal studies of these drugs have shown upregulation of ACE2, which facilitates the entry of the SARS-CoV-2 virus into human cells.
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Already, multiple studies have examined the effect of ACEI/ARB use on COVID-19. However, no large study has been able to assess how many participants in these studies were actually exposed to SARS-COV-2.
Katrina Armstrong, MD, physician-in-chief in the Department of Medicine at Massachusetts General Hospital; Joshua P. Metlay, MD, PhD, chief of the Division of General Internal Medicine; Jennifer Haas, MD, physician in the Department of Medicine; and colleagues recently conducted the first study of ACEI/ARB use in a large cohort of people known to have household exposure to SARS-CoV-2. Use of either an ACEI or ARB was associated with decreased risk of COVID-19 diagnosis, they report in PLoS One.
The researchers began by identifying 8,672 patients who had a positive polymerase chain reaction test for SARS-CoV-2 within the Mass General Brigham health system between March 4 and May 17, 2020. Geocoding was used to match these individuals to 9,101 people registered in the system who lived at the same address.
1,499 of the household contacts were taking an ACEI or ARB at study entry. All were followed until they had a positive test for SARS-CoV-2 or until June 16, 2020.
Risk of COVID-19
Unadjusted Analysis—Household contacts taking ACEI/ARBs were slightly more likely to be diagnosed with COVID-19 (18.7% vs. 15.0%; P=0.00) than contacts not taking those medications. That result probably reflected the older age and greater comorbidity burden of people using ACEIs/ARBs.
Multivariable analysis—After adjustment for age, gender, race/ethnicity, English proficiency, comorbid conditions and date of study entry, ACEI/ARB use was associated with a significantly decreased risk of being diagnosed with COVID-19 (OR, 0.60; 95% CI, 0.44–0.81; P=0.00). The results were similar when ACEI and ARB use were analyzed separately.
The strength of the association between ACEI/ARB use and decreased COVID-19 risk was similar in all subgroups studied: diagnosis of hypertension, diabetes or cardiovascular disease; age ≥65; and body mass index ≥30. No other medication classes were associated with a reduced risk of COVID-19.
Support for the Current Guidance
Results from this observational study do not prove ACEIs/ARBs protect against COVID-19. However, they support the current professional society recommendations that the use of these medications should not be discontinued because of concern about COVID-19.
It's important to understand that entry of SARS-CoV-2 into cells requires not just ACE2 but also transmembrane protease serine 2, which is not affected by ACEI/ARB use. Furthermore, binding of the SARS-CoV-2 spike protein to ACE2 has been shown to downregulate ACE2, leading to overactivation of angiotensin II, which has potent vasoconstrictive and proinflammatory effects. Thus, higher levels of ACE2 may be helpful in SARS-CoV-2–infected patients.
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