scholarly journals Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic

2021 ◽  
Vol 12 ◽  
Author(s):  
Simon B. Gressens ◽  
Georges Leftheriotis ◽  
Jean-Claude Dussaule ◽  
Martin Flamant ◽  
Bernard I. Levy ◽  
...  

Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.

2020 ◽  
Vol 7 ◽  
Author(s):  
Sherry-Ann Brown ◽  
Svetlana Zaharova ◽  
Peter Mason ◽  
Jonathan Thompson ◽  
Bicky Thapa ◽  
...  

Overlapping commonalities between coronavirus disease of 2019 (COVID-19) and cardio-oncology regarding cardiovascular toxicities (CVT), pathophysiology, and pharmacology are special topics emerging during the pandemic. In this perspective, we consider an array of CVT common to both COVID-19 and cardio-oncology, including cardiomyopathy, ischemia, conduction abnormalities, myopericarditis, and right ventricular (RV) failure. We also emphasize the higher risk of severe COVID-19 illness in patients with cardiovascular disease (CVD) or its risk factors or cancer. We explore commonalities in the underlying pathophysiology observed in COVID-19 and cardio-oncology, including inflammation, cytokine release, the renin-angiotensin-aldosterone-system, coagulopathy, microthrombosis, and endothelial dysfunction. In addition, we examine common pharmacologic management strategies that have been elucidated for CVT from COVID-19 and various cancer therapies. The use of corticosteroids, as well as antibodies and inhibitors of various molecules mediating inflammation and cytokine release syndrome, are discussed. The impact of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) is also addressed, since these drugs are used in cardio-oncology and have received considerable attention during the COVID-19 pandemic, since the culprit virus enters human cells via the angiotensin converting enzyme 2 (ACE2) receptor. There are therefore several areas of overlap, similarity, and interaction in the toxicity, pathophysiology, and pharmacology profiles in COVID-19 and cardio-oncology syndromes. Learning more about either will likely provide some level of insight into both. We discuss each of these topics in this viewpoint, as well as what we foresee as evolving future directions to consider in cardio-oncology during the pandemic and beyond. Finally, we highlight commonalities in health disparities in COVID-19 and cardio-oncology and encourage continued development and implementation of innovative solutions to improve equity in health and healing.


2020 ◽  
Vol 25 (6) ◽  
pp. 503-507 ◽  
Author(s):  
Husam M. Salah ◽  
Guisseppe Calcaterra ◽  
Jawahar L. Mehta

To determine the effect renin-angiotensin system blockers on the outcome in patients with hypertension and concurrent COVID-19 infection, we searched PubMed, the Cochrane Library, and Google Scholar for relevant articles. Twelve studies with a total of 16,101 patients met the inclusion criteria. The mortality rate among the users of angiotensin converting enzyme inhibitors or angiotensin receptor blockers was 12.15% and in non-users it was 14.56% (risk ratio 0.70, 95% CI [0.53-0.91], P < 0.007). There was no difference in the risk of death between the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (risk ratio 1.09, 95% CI [0.90 -1.32]). We conclude that the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers improves mortality in patients with hypertension and concurrent COVID-19 infection, without a significant difference between ACEIs and ARBs in this population.


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