Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.

<h4>Aims</h4>Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system...

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Autores principales:	Sebastian Cremer, Lisa Pilgram, Alexander Berkowitsch, Melanie Stecher, Siegbert Rieg, Mariana Shumliakivska, Denisa Bojkova, Julian Uwe Gabriel Wagner, Galip Servet Aslan, Christoph Spinner, Guillermo Luxán, Frank Hanses, Sebastian Dolff, Christiane Piepel, Clemens Ruppert, Andreas Guenther, Maria Madeleine Rüthrich, Jörg Janne Vehreschild, Kai Wille, Martina Haselberger, Hanno Heuzeroth, Arne Hansen, Thomas Eschenhagen, Jindrich Cinatl, Sandra Ciesek, Stefanie Dimmeler, Stefan Borgmann, Andreas Zeiher, LEOSS study group
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e234542cdff42628f85dca9a1f5a0e7
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spelling	oai:doaj.org-article:7e234542cdff42628f85dca9a1f5a0e72021-12-02T20:07:48ZAngiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.1932-620310.1371/journal.pone.0258684https://doaj.org/article/7e234542cdff42628f85dca9a1f5a0e72021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258684https://doaj.org/toc/1932-6203<h4>Aims</h4>Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.<h4>Methods and results</h4>We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59-0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43-0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.<h4>Conclusion</h4>These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.Sebastian CremerLisa PilgramAlexander BerkowitschMelanie StecherSiegbert RiegMariana ShumliakivskaDenisa BojkovaJulian Uwe Gabriel WagnerGalip Servet AslanChristoph SpinnerGuillermo LuxánFrank HansesSebastian DolffChristiane PiepelClemens RuppertAndreas GuentherMaria Madeleine RüthrichJörg Janne VehreschildKai WilleMartina HaselbergerHanno HeuzerothArne HansenThomas EschenhagenJindrich CinatlSandra CiesekStefanie DimmelerStefan BorgmannAndreas ZeiherLEOSS study groupPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258684 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sebastian Cremer Lisa Pilgram Alexander Berkowitsch Melanie Stecher Siegbert Rieg Mariana Shumliakivska Denisa Bojkova Julian Uwe Gabriel Wagner Galip Servet Aslan Christoph Spinner Guillermo Luxán Frank Hanses Sebastian Dolff Christiane Piepel Clemens Ruppert Andreas Guenther Maria Madeleine Rüthrich Jörg Janne Vehreschild Kai Wille Martina Haselberger Hanno Heuzeroth Arne Hansen Thomas Eschenhagen Jindrich Cinatl Sandra Ciesek Stefanie Dimmeler Stefan Borgmann Andreas Zeiher LEOSS study group Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.
description	<h4>Aims</h4>Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.<h4>Methods and results</h4>We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59-0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43-0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.<h4>Conclusion</h4>These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.
format	article
author	Sebastian Cremer Lisa Pilgram Alexander Berkowitsch Melanie Stecher Siegbert Rieg Mariana Shumliakivska Denisa Bojkova Julian Uwe Gabriel Wagner Galip Servet Aslan Christoph Spinner Guillermo Luxán Frank Hanses Sebastian Dolff Christiane Piepel Clemens Ruppert Andreas Guenther Maria Madeleine Rüthrich Jörg Janne Vehreschild Kai Wille Martina Haselberger Hanno Heuzeroth Arne Hansen Thomas Eschenhagen Jindrich Cinatl Sandra Ciesek Stefanie Dimmeler Stefan Borgmann Andreas Zeiher LEOSS study group
author_facet	Sebastian Cremer Lisa Pilgram Alexander Berkowitsch Melanie Stecher Siegbert Rieg Mariana Shumliakivska Denisa Bojkova Julian Uwe Gabriel Wagner Galip Servet Aslan Christoph Spinner Guillermo Luxán Frank Hanses Sebastian Dolff Christiane Piepel Clemens Ruppert Andreas Guenther Maria Madeleine Rüthrich Jörg Janne Vehreschild Kai Wille Martina Haselberger Hanno Heuzeroth Arne Hansen Thomas Eschenhagen Jindrich Cinatl Sandra Ciesek Stefanie Dimmeler Stefan Borgmann Andreas Zeiher LEOSS study group
author_sort	Sebastian Cremer
title	Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.
title_short	Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.
title_full	Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.
title_fullStr	Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.
title_full_unstemmed	Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.
title_sort	angiotensin ii receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and covid-19 disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7e234542cdff42628f85dca9a1f5a0e7
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Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.

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