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

  • 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.

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Author:Sebastian CremerORCiDGND, Lisa PilgramGND, Alexander BerkowitschGND, Melanie StecherORCiDGND, Siegbert RiegGND, Mariana ShumliakivskaORCiD, Denisa BojkovaORCiDGND, Julian Uwe Gabriel WagnerORCiDGND, Galip Servet AslanGND, Christoph Daniel SpinnerORCiDGND, Guillermo LuxánORCiD, Frank HansesGND, Sebastian Conrad Johannes DolffORCiDGND, Christiane PiepelGND, Clemens RuppertGND, Andreas GüntherORCiDGND, Maria Madeleine RüthrichGND, Jörg Janne VehreschildORCiDGND, Kai WilleGND, Martina Maria HaselbergerORCiDGND, Hanno HeuzerothGND, Arne HansenGND, Thomas EschenhagenGND, Jindrich CinatlORCiDGND, Sandra CiesekORCiDGND, Stefanie DimmelerORCiDGND, Stefan BorgmannGND, Andreas M. ZeiherORCiDGND
URN:urn:nbn:de:hebis:30:3-627113
DOI:https://doi.org/10.1371/journal.pone.0258684
ISSN:1932-6203
Parent Title (English):PLOS ONE
Publisher:PLOS
Place of publication:San Francisco, California, US
Document Type:Article
Language:English
Date of Publication (online):2021/10/21
Date of first Publication:2021/10/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:LEOSS study group
Release Date:2024/02/26
Tag:Biomarkers; COVID 19; Cardiovascular disease risk; Cardiovascular diseases; Hypertension; Inflammation; Multivariate analysis; SARS CoV 2
Volume:16
Issue:10, art. e0258684
Article Number:e0258684
Page Number:17
First Page:1
Last Page:17
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International