In this multicenter blinded RCT for outpatients with mild symptomatic COVID-19 disease, losartan did not reduce hospitalizations, though assessment was limited by low event rate. Importantly, viral load was not statistically affected by treatment. This study does not support initiation of losartan for low-risk outpatients.
Normally, ACE2 is found on lung, kidney, heart, and gut cells. But scientists recently found ACE2 receptors on the cells in peoples’ noses — an “aha” moment for people like Farzen who had studied the 2003-era SARS virus.
“It was never quite clear how the virus trafficked all the way to the lower respiratory tract to give you this horrendous pneumonia,” he said.
In the search for treatments for COVID-19, many researchers are focusing their attention on a specific protein that allows the virus to infect human cells. Called the angiotensin-converting enzyme 2, or ACE2 “receptor,” the protein provides the entry point for the coronavirus to hook into and infect a wide range of human cells. Might this be central in how to treat this disease?
Despite initial fears, evidence from retrospective observational studies supports the inhibition of the renin-angiotensin system as an emerging pathway to delay or moderate angiotensin II-driven lung inflammation. This has triggered several prospective clinical trials.
Pedrosa et al. (Clin. Sci. (Lond.) (2021), 135, 465–481) showed in rats that captopril and candesartan up-regulated ACE2 expression and the protective RAS pathway in lung tissue. In culture of pneumocytes, the captopril/candesartan-induced ACE2 up-regulation was associated with inhibition of ADAM17 activity, counterbalancing increased ACE2 expression, which was associated with reduced SARS-CoV-2 spike protein entry. If confirmed in humans, these results could become the pathophysiological background for justifying RAS inhibitors as cornerstone cardiovascular protectives even during COVID-19 pandemic.
There is little evidence that antihypertensive drugs worsen COVID-19, and scientists are instead exploring the idea that such medications—or their downstream effects—may actually alleviate symptoms.
There is low-certainty evidence that patients on long-term therapy with ACE inhibitors or ARBs are not at higher risk of poor outcomes from COVID-19.
While it should not be assumed that we have a complete picture of SARS-CoV-2 mechanism of infection and its interaction with ACE2, much has been learned with clear therapeutic implications. Potential therapies aimed at intercepting SARS-CoV-2 from reaching the full-length membrane-bound ACE2 receptor using soluble ACE2 protein and other potential approaches are briefly discussed as well.
Widely prescribed cardiovascular drugs, some recently suspected in high death rates of infected patients, now are being studied for potential protection