Abstract
Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.
Highlights
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is a major public health problem
The mRNA expressions of two inflammatory factors (IL-6 and TNFα) were decreased in the lung, kidney, and heart of AT1 receptor (AT1R) blocker-treated hypertensive hACE2 transgenic mice (Fig. 3c). These results indicate that AT1R blocker treatment decreases the inflammatory reaction in hypertensive hACE2 transgenic mice with SARS-CoV-2 infection, which may justify its use in hypertensive patients infected with SARS-CoV-2
We found that SARS-CoV-2 viral load in the heart and kidney of normotensive hACE2 transgenic mice was increased by AT1R blocker treatment at 1 dpi
Summary
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is a major public health problem. Retrospective studies found that hospitalized hypertensive patients with SARS-CoV-2 infection treated with ACE inhibitors or AT1R blockers have a lower risk of all-cause mortality than those treated with other drugs [13]. Due to ACE2 is critically important in the cellular entry of SARS and SARS-CoV-2, it is possible that hypertensive COVID-19 patients treated with drugs that increase ACE2, e.g., ACE inhibitors and AT1R blockers, are at a higher risk for the development and severity SARS-CoV-2 infection [15]. Human (h) ACE2 transgenic mice, intranasally inoculated with SARS-CoV-2, develop severe pulmonary pathology with viral replication in the lungs and intestines, at 1-day post infection (dpi) and severe pulmonary pathology 5 dpi. The effect of AT1R blockers in hypertensive hACE2 transgenic mice, induced by angiotensin II and infected with SARS-CoV-2, has not been studied. We studied hospitalized COVID-19 hypertensive patients and hypertensive hACE2 transgenic mice to determine whether AT1R blockers protect or promote the development of COVID-19 [17]
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