COVID-19 and Renin Angiotensin Blockers
Franz H. Messerli, George C.M. Siontis, Emrush Rexhaj
Abstract
oth angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have repeatedly, but not consistently, been documented to slow progression of pulmonary complications in vulnerable patients.A previously published meta-analysis pointed toward a putative protective role of ACEIs, and to lesser extent of ARBs, in risk of community acquired pneumonia.ACEIs in 7 studies were associated with decreased pneumonia mortality compared with control treatment (odds ratio [OR] 0.66 [95% CI, 0.55-0.80]).ARBs in 1 randomized controlled trial only showed a reduction of borderline significance (OR 0.63 [95% CI, 0.40-1.00]). 1 These seemingly beneficial findings of renin angiotensin system (RAS) blockade on outcomes in pneumonia resurfaced in the recent literature in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), infection.Several potential therapeutic/preventive approaches to address angiotensin-converting enzyme 2 (ACE2)-mediated COVID-19 have been described, including the suggestion that ARBs could be administered in the form of a nasal spray to treat COVID-19.Because pneumonia is a common potentially fatal complication in COVID-19 infection, we wondered whether RAS blockade could exert a favorable effect on pneumonia-related outcomes. EVIDENCE OF ACEI/ARB THERAPY AND VIRAL INFECTIONS OF RESPIRATORY SYSTEMWe systematically reviewed the literature for evidence from animal models and clinical data related to the role of ACEIs/ARBs and viral infections.We searched PubMed and EMBASE for original research on animals or humans investigating the impact of ACEIs/ARBs on viral infections.The following search terms were used: viral, virus, infect, pneumonia, acute respiratory distress syndrome, acute lung injury, and angiotensin.Overall, we identified 4 studies 2-5 evaluating the role of ACEIs/ ARBs in viral infections of respiratory system.In 3 studies of animal models, 2-4 virusinduced lung injury and the role of losartan was tested; all reported a key role of decreased RAS activation through losartan (Table ).In 1 retrospective study, 5 lower rates of death and intubation were noted among patients who continued to be on ACEIs during hospitalization (OR 0.25 [95% CI, 0.09-0.64]).We did not find evidence supporting the continuation, withdrawal, or de novo initiation of ACEIs/ ARBs in patients with SARS-CoV-2-infection. COVID-19 AND HYPERTENSIONEpidemiological data suggest that patients with cardiovascular disease and hypertension are more susceptible to SARS-CoV-2-infection and that the course of pneumonia is more severe in hypertensive relative to normotensive subjects.