Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic
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 c...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.624052/full |
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| author | Simon B. Gressens Georges Leftheriotis Jean-Claude Dussaule Jean-Claude Dussaule Martin Flamant Martin Flamant Bernard I. Levy Emmanuelle Vidal-Petiot Emmanuelle Vidal-Petiot |
| author_facet | Simon B. Gressens Georges Leftheriotis Jean-Claude Dussaule Jean-Claude Dussaule Martin Flamant Martin Flamant Bernard I. Levy Emmanuelle Vidal-Petiot Emmanuelle Vidal-Petiot |
| author_sort | Simon B. Gressens |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T10:29:57Z |
| format | Article |
| id | doaj.art-829e780ea95c45a8a5868deee785e32c |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-14T10:29:57Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-829e780ea95c45a8a5868deee785e32c2022-12-21T23:06:10ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-02-011210.3389/fphys.2021.624052624052Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 PandemicSimon B. Gressens0Georges Leftheriotis1Jean-Claude Dussaule2Jean-Claude Dussaule3Martin Flamant4Martin Flamant5Bernard I. Levy6Emmanuelle Vidal-Petiot7Emmanuelle Vidal-Petiot8Department of Infectious and Tropical Diseases, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, FranceLaboratory of Molecular Physiology and Medicine, Université Cote d’Azur, Nice, FranceSorbonne Université, INSERM, Unité des Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée, AP-HP, Hôpital Tenon, Paris, FranceFaculty of Medicine, Sorbonne University, Paris, FranceDepartment of Physiology, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, FranceInserm U1149, Centre for Research on Inflammation, Université de Paris, Paris, FranceInserm U970, PARCC, Paris, FranceDepartment of Physiology, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, FranceInserm U1149, Centre for Research on Inflammation, Université de Paris, Paris, FranceSince 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.https://www.frontiersin.org/articles/10.3389/fphys.2021.624052/fullSARS-CoV-2COVID-19renin-angiotensin-aldosterone systemRAAS blockersangiotensin converting enzyme inhibitorsangiotensin receptor blockers |
| spellingShingle | Simon B. Gressens Georges Leftheriotis Jean-Claude Dussaule Jean-Claude Dussaule Martin Flamant Martin Flamant Bernard I. Levy Emmanuelle Vidal-Petiot Emmanuelle Vidal-Petiot Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic Frontiers in Physiology SARS-CoV-2 COVID-19 renin-angiotensin-aldosterone system RAAS blockers angiotensin converting enzyme inhibitors angiotensin receptor blockers |
| title | Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic |
| title_full | Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic |
| title_fullStr | Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic |
| title_full_unstemmed | Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic |
| title_short | Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic |
| title_sort | controversial roles of the renin angiotensin system and its modulators during the covid 19 pandemic |
| topic | SARS-CoV-2 COVID-19 renin-angiotensin-aldosterone system RAAS blockers angiotensin converting enzyme inhibitors angiotensin receptor blockers |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.624052/full |
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