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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

Cremer, S., Pilgram, L., Berkowitsch, A., Stecher, M., Rieg, S., Shumliakivska, M., et al. (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): e0258684. doi:10.1371/journal.pone.0258684.

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 Creators:
Cremer, Sebastian, Author
Pilgram, Lisa, Author
Berkowitsch, Alexander, Author
Stecher, Melanie, Author
Rieg, Siegbert, Author
Shumliakivska, Mariana, Author
Bojkova, Denisa, Author
Wagner, Julian Uwe Gabriel, Author
Aslan, Galip Servet1, Author              
Spinner, Christoph, Author
Luxan, Guillermo, Author
Hanses, Frank, Author
Dolff, Sebastian, Author
Piepel, Christiane, Author
Ruppert, Clemens, Author
Guenther, Andreas, Author
Ruthrich, Maria Madeleine, Author
Vehreschild, Jorg Janne, Author
Wille, Kai, Author
Haselberger, Martina, Author
Heuzeroth, Hanno, AuthorHansen, Arne, AuthorEschenhagen, Thomas, AuthorCinatl, Jindrich, AuthorCiesek, Sandra, AuthorDimmeler, Stefanie, AuthorBorgmann, Stefan, AuthorZeiher, Andreas, Author more..
Affiliations:
1IMPRS, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_3242057              

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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.

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 Dates: 2021-10-21
 Publication Status: Published online
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Title: PLOS ONE
Source Genre: Journal
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Pages: - Volume / Issue: 16 (10) Sequence Number: e0258684 Start / End Page: - Identifier: ISSN: 1932-6203