Cremer, Sebastian, Pilgram, Lisa, Berkowitsch, Alexander, Stecher, Melanie, Rieg, Siegbert, Shumliakivska, Mariana, Bojkova, Denisa, Wagner, Julian Uwe Gabriel ORCID: 0000-0002-3863-854X, Aslan, Galip Servet ORCID: 0000-0002-5084-1241, Spinner, Christoph, Luxan, Guillermo, Hanses, Frank, Dolff, Sebastian, Piepel, Christiane, Ruppert, Clemens, Guenther, Andreas, Ruthrich, Maria Madeleine, Vehreschild, Jorg Janne, Wille, Kai ORCID: 0000-0002-7682-8563, Haselberger, Martina, Heuzeroth, Hanno, Hansen, Arne, Eschenhagen, Thomas, Cinatl, Jindrich, Ciesek, Sandra, Dimmeler, Stefanie, Borgmann, Stefan and Zeiher, Andreas (2021). Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease. PLoS One, 16 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Aims 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. Methods and results 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. Conclusion 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Cremer, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pilgram, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berkowitsch, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stecher, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rieg, SiegbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shumliakivska, MarianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bojkova, DenisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, Julian Uwe GabrielUNSPECIFIEDorcid.org/0000-0002-3863-854XUNSPECIFIED
Aslan, Galip ServetUNSPECIFIEDorcid.org/0000-0002-5084-1241UNSPECIFIED
Spinner, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luxan, GuillermoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hanses, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dolff, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piepel, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruppert, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenther, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruthrich, Maria MadeleineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vehreschild, Jorg JanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wille, KaiUNSPECIFIEDorcid.org/0000-0002-7682-8563UNSPECIFIED
Haselberger, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heuzeroth, HannoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, ArneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eschenhagen, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cinatl, JindrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ciesek, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dimmeler, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borgmann, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeiher, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-602902
DOI: 10.1371/journal.pone.0258684
Journal or Publication Title: PLoS One
Volume: 16
Number: 10
Date: 2021
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACE2; EXPRESSIONMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60290

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