According to a nationwide US observational analysis, ACE inhibitors may be clinically protective against the development of severe illness in SARS-CoV-2 older patients. Moreover, a novel meta-analysis has demonstrated that ACE inhibitors and ARBs (angiotensin-receptor blockers) are not related to more severe disease and do not elevate susceptibility to infection in COVID-19 patients. 

In another analysis, data from 10,000 US SARS-CoV-2 virus patients, who were registered in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for anti-hypertensives was examined.

The study results demonstrated that for older people enrolled in Medicare Advantage plans, ACE inhibitors were associated with an almost 40% minimized risk for COVID-19 hospitalization. No such benefit was witnessed in either group with ARBs or in the younger commercially insured patients.

A trial is being planned in which 10,000 older COVID-19 people will be randomly allocated to receive either placebo or a low dose of an ACE inhibitor. Trial recruitment will initiate soon. It is open to all eligible Americans (older than 50 years, tested negative for COVID-19, and not on anti-hypertensives).

In a propensity score-matched study, neither ACE inhibitors nor ARBs were substantially associated with hospitalization risk. However, in analyses by an insurance group, ACE inhibitors (but not ARBs) were associated with considerably lower hospitalization risk among the Medicare group but not among the commercially insured group.

Another study examined the outcomes of 7933 hypertensive individuals hospitalized for COVID-19 (92% Medicare Advantage patients). The use of neither an ACE inhibitor nor an ARB was linked with the in-hospital mortality risk. There is diminished pneumonia risk with ACE inhibitors that are not witnessed with ARBs. In patients aged 65 or older, ACE inhibitors may be highly protective. But, in patients below 65 age, it may be harmful. ACE inhibitors may protect against the development of acute lung injury in COVID-19 infected patients. By binding to the ACE enzyme, ACE inhibitors may hamper the enzyme's uptake of the SARS-CoV-2 virus.

ACE inhibitors (but not ARBs) are closely linked with ACE2 receptors upregulation, which modulates local interactions of the renin-angiotensin-aldosterone system in the tissues of the lungs. Both ACE inhibitors and ARBs elevate the ACE2 enzyme level to which the coronavirus binds in the lungs. ARBs impede angiotensin II effects. This elevates angiotensin II levels that lead to the upregulation of ACE2 production.

In a meta-analysis, high-certainty evidence suggested that the use of ACE inhibitors or ARB is not linked with a more severe COVID-19 pandemic. Moderate certainty evidence illustrated that among symptomatic individuals no connection exists between these medications and positive SARS-CoV-2 test results.