Modulation of the renin-angiotensin system against COVID-19: A path forward?

Soon after the pandemic outbreak in 2020, it was proposed that binding of SARS-CoV-2 to the angiotensin converting enzyme-2 may explain most of COVID-19’s manifestations. Therefore, manipulation of the renin-angiotensin system (RAS) by using well known and commercialized blockers of its classical ar...

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Main Authors: Serge Camelo, Waly Dioh, J. Pedro Teixeira, Laurence W. Busse, Girish Nair, Gaëtan Plantefeve, Capucine Morelot-Panzini, Suzana Margareth Lobo, Wesley H. Self, Sean P. Collins, Rob Van Maanen, Stanislas Veillet
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:International Journal of Infectious Diseases
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Online Access:http://www.sciencedirect.com/science/article/pii/S1201971225000906
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author Serge Camelo
Waly Dioh
J. Pedro Teixeira
Laurence W. Busse
Girish Nair
Gaëtan Plantefeve
Capucine Morelot-Panzini
Suzana Margareth Lobo
Wesley H. Self
Sean P. Collins
Rob Van Maanen
Stanislas Veillet
author_facet Serge Camelo
Waly Dioh
J. Pedro Teixeira
Laurence W. Busse
Girish Nair
Gaëtan Plantefeve
Capucine Morelot-Panzini
Suzana Margareth Lobo
Wesley H. Self
Sean P. Collins
Rob Van Maanen
Stanislas Veillet
author_sort Serge Camelo
collection DOAJ
description Soon after the pandemic outbreak in 2020, it was proposed that binding of SARS-CoV-2 to the angiotensin converting enzyme-2 may explain most of COVID-19’s manifestations. Therefore, manipulation of the renin-angiotensin system (RAS) by using well known and commercialized blockers of its classical arm or by repurposing new stimulators of the alternative RAS pathway in clinical development was seen as a potentially effective strategy for the treatment of COVID-19. Moreover, this therapeutic approach had previously shown significant promise in the treatment of other respiratory viral respiratory infections and forms of acute respiratory distress syndrome. Consequently, several randomized clinical trials (RCTs) were launched to test the efficacy of rebalancing the RAS to reduce the severity of COVID-19. While most of these trials produced neutral results, certain studies reached their primary endpoints. In the present collaborative review, sponsors and main investigators of some of these trials attempt to reach a consensus regarding their clinical significance and which factors influenced their differing outcomes. The knowledge gained through the careful analysis of these RCTs of RAS modulators in patients with severe COVID-19 may prove useful for other forms of acute lung injury.
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publisher Elsevier
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series International Journal of Infectious Diseases
spelling doaj-art-e01dfddef45b453d9c73bf0578aa453d2025-08-20T02:09:29ZengElsevierInternational Journal of Infectious Diseases1201-97122025-05-0115410786710.1016/j.ijid.2025.107867Modulation of the renin-angiotensin system against COVID-19: A path forward?Serge Camelo0Waly Dioh1J. Pedro Teixeira2Laurence W. Busse3Girish Nair4Gaëtan Plantefeve5Capucine Morelot-Panzini6Suzana Margareth Lobo7Wesley H. Self8Sean P. Collins9Rob Van Maanen10Stanislas Veillet11Biophytis, Sorbonne Université, Paris, France; Corresponding authorBiophytis, Sorbonne Université, Paris, FranceDivisions of Nephrology and Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of New Mexico School of Medicine MSC10-5550, 1 University of New Mexico, Albuquerque, New Mexico, USADivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, USAOUWB School of Medicine, William Beaumont Hospital, Royal Oak, Michigan, USARéanimation Polyvalente, CH DUPOUY, Argenteuil, FranceSorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France; AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, hôpital Pitié-Salpêtrière, Service de Pneumologie (Département R3S), Paris, FranceIntensive Care Division, Hospital de Base, Faculdade de Medicina de São José do Rio Preto - São José do Rio Preto (Sao Paulo), BrazilDepartment of Emergency Medicine and Vanderbilt University Medical Center Veterans Affairs Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Nashville, Tennessee, USADepartment of Emergency Medicine and Vanderbilt University Medical Center Veterans Affairs Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Nashville, Tennessee, USABiophytis, Sorbonne Université, Paris, FranceBiophytis, Sorbonne Université, Paris, FranceSoon after the pandemic outbreak in 2020, it was proposed that binding of SARS-CoV-2 to the angiotensin converting enzyme-2 may explain most of COVID-19’s manifestations. Therefore, manipulation of the renin-angiotensin system (RAS) by using well known and commercialized blockers of its classical arm or by repurposing new stimulators of the alternative RAS pathway in clinical development was seen as a potentially effective strategy for the treatment of COVID-19. Moreover, this therapeutic approach had previously shown significant promise in the treatment of other respiratory viral respiratory infections and forms of acute respiratory distress syndrome. Consequently, several randomized clinical trials (RCTs) were launched to test the efficacy of rebalancing the RAS to reduce the severity of COVID-19. While most of these trials produced neutral results, certain studies reached their primary endpoints. In the present collaborative review, sponsors and main investigators of some of these trials attempt to reach a consensus regarding their clinical significance and which factors influenced their differing outcomes. The knowledge gained through the careful analysis of these RCTs of RAS modulators in patients with severe COVID-19 may prove useful for other forms of acute lung injury.http://www.sciencedirect.com/science/article/pii/S1201971225000906COVID-19Renin-angiotensin systemAngiotensin type 1 receptorAngiotensin-IIAngiotensin-(1-7)Mas receptor
spellingShingle Serge Camelo
Waly Dioh
J. Pedro Teixeira
Laurence W. Busse
Girish Nair
Gaëtan Plantefeve
Capucine Morelot-Panzini
Suzana Margareth Lobo
Wesley H. Self
Sean P. Collins
Rob Van Maanen
Stanislas Veillet
Modulation of the renin-angiotensin system against COVID-19: A path forward?
International Journal of Infectious Diseases
COVID-19
Renin-angiotensin system
Angiotensin type 1 receptor
Angiotensin-II
Angiotensin-(1-7)
Mas receptor
title Modulation of the renin-angiotensin system against COVID-19: A path forward?
title_full Modulation of the renin-angiotensin system against COVID-19: A path forward?
title_fullStr Modulation of the renin-angiotensin system against COVID-19: A path forward?
title_full_unstemmed Modulation of the renin-angiotensin system against COVID-19: A path forward?
title_short Modulation of the renin-angiotensin system against COVID-19: A path forward?
title_sort modulation of the renin angiotensin system against covid 19 a path forward
topic COVID-19
Renin-angiotensin system
Angiotensin type 1 receptor
Angiotensin-II
Angiotensin-(1-7)
Mas receptor
url http://www.sciencedirect.com/science/article/pii/S1201971225000906
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