key: cord-0924391-vbwix0fw authors: Ateya, Areej Mohamed; Sabri, Nagwa A. title: Angiotensin‐converting enzyme inhibitors and angiotensin‐receptor blockers benefits outweigh the risks in COVID‐19 hypertensive patients date: 2020-11-22 journal: J Med Virol DOI: 10.1002/jmv.26672 sha: 17ecfdf9be93ac791a5fda6873f8dcfe02a9d4c4 doc_id: 924391 cord_uid: vbwix0fw We read with interest the article published by Wang et al. in Medical Virology journal This article is protected by copyright. All rights reserved. Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers benefits outweigh the risks in COVID-19 hypertensive patients infected hypertensive patients. We are in total agreement with these findings and we want to represent the mechanisms that can support these results. ACE2 receptor is the key mediator for viral entry into the human cells. Meanwhile, it is an important regulator of the renin-angiotensinaldosterone system, that acts by hydrolyzing angiotensin I to angiotensin (1-9) and angiotensin II to angiotensin (1-7). The dual roles played by ACE2 as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as a protector against the harmful effects of angiotensin II, has caused controversy regarding the continued use of ACEIs and ARBs during the outbreak as they result in ACE2 receptor upregulation. 2 Recently, recommendations have been released supporting the continued use of these potential antihypertensive agents throughout the pandemic due to insufficient evidence of their harmful effects. 3, 4 We hypothesize that ACEIs and ARBs use for COVID-19 hypertensive patients provide more benefits than harms and might be the drug of choice for both blood pressure control and viral treatment. First, cytokine storm syndrome, characterized by increased inflammatory mediators is considered one of the main causes of increased mortality associating COVID-19. 5 The anti-inflammatory and pleiotropic effects of ACEIs and ARBs have been proven in patients with hypertension and coronary heart disease. This supports the beneficial impact of ACEs and ARBs on the novel virus rather than harm. 6 Second, COVID-19 infection is associated with cardiovascular complications in many patients which are more common among hypertensive patients. Although, the underlying mechanism remains incompletely understood, endothelial dysfunction seems to represent the primary step in COVID-19 associated cardiovascular risk due to ACE2 expression on endothelial cells. 7 Studies in patients with cardiovascular diseases have demonstrated improved flow-mediated dilatation, a marker of endothelial function with ACEIs and ARBs use, providing convincing evidence of their potential benefits on endothelial dysfunction. 8, 9 Third, coagulopathy has been manifested in up to 50% of COVID-19 severe cases especially the hypertensive patients. By downregulating the ACE2, SARS-COV-2 increases angiotensin II, that in turn, increases thrombin formation and impairs fibrinolysis. 10 Recent in vitro and in vivo studies support the anti-thrombotic and fibrinolytic characteristics of ACEIs and ARBs. 11, 12 In conclusion, the benefits of ACEIs and ARBs use during COVID-19 can greatly outweigh the risks, which supports Wang et al. findings. In the absence of a suitable vaccine and while facing a viral second wave, some clinical trials are underway to evaluate the possibility of using these already FDA approved medications for treatment of the novel virus, especially in hypertensive patients that represent a well-established risk category for the infection. The use of renin-angiotensin-aldosterone system (RAAS) inhibitors is associated with a lower risk of mortality in hypertensive COVID-19 patients: a systematic review and meta-analysis Update on the renin-angiotensin-aldosterone system in pediatric kidney disease and its interactions with coronavirus Professional Heart Daily. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19 5836_HFSAACCAHA-statement-addresses-concerns-re-using-RAAS-ant agonists-in-COVID-19 Position statement of the ESC Council on hypertension on ACE-inhibitors and angiotensin receptor blockers Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade Endothelial cell infection and endotheliitis in COVID-19 Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials Effect of different classes of antihypertensive drugs on endothelial function and inflammation Pathological role of angiotensin II in severe COVID-19 The antithrombotic effect of captopril and losartan on experimental arterial thrombosis in rats Potential antithrombotic and fibrinolytic properties of the angiotensin converting enzyme inhibitors