Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study
Abstract Background Acute respiratory distress syndrome (ARDS) associated with coronavirus infectious disease (COVID)-19 has been a challenge in intensive care medicine for the past three years. Dysregulation of the renin–angiotensin system (RAS) is linked to COVID-19, but also to non-COVID-19 ARDS....
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SpringerOpen
2025-01-01
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| Series: | Annals of Intensive Care |
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| Online Access: | https://doi.org/10.1186/s13613-025-01433-3 |
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| author | Katharina Krenn Felix Kraft Luana Mandroiu Verena Tretter Roman Reindl-Schwaighofer Theresa Clement Oliver Domenig Matthias G. Vossen Gregor Riemann Marko Poglitsch Roman Ullrich |
| author_facet | Katharina Krenn Felix Kraft Luana Mandroiu Verena Tretter Roman Reindl-Schwaighofer Theresa Clement Oliver Domenig Matthias G. Vossen Gregor Riemann Marko Poglitsch Roman Ullrich |
| author_sort | Katharina Krenn |
| collection | DOAJ |
| description | Abstract Background Acute respiratory distress syndrome (ARDS) associated with coronavirus infectious disease (COVID)-19 has been a challenge in intensive care medicine for the past three years. Dysregulation of the renin–angiotensin system (RAS) is linked to COVID-19, but also to non-COVID-19 ARDS. It is still unclear whether changes in the RAS are associated with prognosis of severe COVID-19. Methods In this prospective exploratory study, blood samples of 94 patients with COVID-19 were taken within 48 h of admission to a medical ward or an ICU. In ICU patients, another blood sample was taken seven days later. Angiotensin (Ang) I-IV, Ang 1–7, Ang 1–5 and aldosterone concentrations were measured with liquid chromatography tandem mass spectrometry (LC–MS/MS) followed by calculation of markers for activities of renin (PRA-S) and ACE (ACE-S), alternative RAS activation (ALT-S) as well as the ratio of aldosterone to Ang II (AA2R). Angiotensin-converting enzyme (ACE) and ACE2 concentrations were measured by LC–MS/MS-based assays. All RAS parameters were evaluated as predictors of 28-day and 60-day survival using receiver operating characteristic and multivariate logistic regression analysis. Results AA2R at inclusion was a predictor of 60-day survival for ICU patients with an AUROC of 0.73. Ang II and active ACE2 were inversely associated with survival (OR 0.07; 95%CI 0.01, 0.39 and OR 0.10; 95%CI 0.01, 0.63) while higher Ang 1–7 predicted favorable outcome (OR 6.8; 95%CI 1.5, 39.9). ICU patients showed higher concentrations of all measured angiotensin metabolites, PRA-S, ALT-S and active ACE2, and lower ACE-S and AA2R than patients in the medical ward at inclusion. After seven days in the ICU, Ang I, Ang II, Ang III and Ang IV concentrations decreased, while ACE and ACE2 levels increased. Ang I, PRA-S, Ang 1–7 and Ang 1–5 concentrations correlated with the SOFA score both at the time of inclusion and after seven days, and driving pressure after seven days. Conclusions AA2R at inclusion predicted 60-day survival with moderate sensitivity, revealing a dissociation between unchanged aldosterone and increased Ang II levels in the most severely ill COVID-19 patients. After adjustment for confounders, Ang 1–7 as the final metabolite of alternative RAS was predictive for survival. |
| format | Article |
| id | doaj-art-34121446b7f5439aa740911861b96b7b |
| institution | Kabale University |
| issn | 2110-5820 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SpringerOpen |
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| series | Annals of Intensive Care |
| spelling | doaj-art-34121446b7f5439aa740911861b96b7b2025-01-19T12:38:33ZengSpringerOpenAnnals of Intensive Care2110-58202025-01-0115111410.1186/s13613-025-01433-3Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory studyKatharina Krenn0Felix Kraft1Luana Mandroiu2Verena Tretter3Roman Reindl-Schwaighofer4Theresa Clement5Oliver Domenig6Matthias G. Vossen7Gregor Riemann8Marko Poglitsch9Roman Ullrich10Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine, Medical University of ViennaDepartment of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine, Medical University of ViennaDepartment of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine, Medical University of ViennaDepartment of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine, Medical University of ViennaDepartment of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of ViennaDepartment of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine, Medical University of ViennaAttoquant Diagnostics GmbHDepartment of Internal Medicine I, Clinical Division of Infectiology, Medical University of ViennaDepartment of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine, Medical University of ViennaAttoquant Diagnostics GmbHDepartment of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine, Medical University of ViennaAbstract Background Acute respiratory distress syndrome (ARDS) associated with coronavirus infectious disease (COVID)-19 has been a challenge in intensive care medicine for the past three years. Dysregulation of the renin–angiotensin system (RAS) is linked to COVID-19, but also to non-COVID-19 ARDS. It is still unclear whether changes in the RAS are associated with prognosis of severe COVID-19. Methods In this prospective exploratory study, blood samples of 94 patients with COVID-19 were taken within 48 h of admission to a medical ward or an ICU. In ICU patients, another blood sample was taken seven days later. Angiotensin (Ang) I-IV, Ang 1–7, Ang 1–5 and aldosterone concentrations were measured with liquid chromatography tandem mass spectrometry (LC–MS/MS) followed by calculation of markers for activities of renin (PRA-S) and ACE (ACE-S), alternative RAS activation (ALT-S) as well as the ratio of aldosterone to Ang II (AA2R). Angiotensin-converting enzyme (ACE) and ACE2 concentrations were measured by LC–MS/MS-based assays. All RAS parameters were evaluated as predictors of 28-day and 60-day survival using receiver operating characteristic and multivariate logistic regression analysis. Results AA2R at inclusion was a predictor of 60-day survival for ICU patients with an AUROC of 0.73. Ang II and active ACE2 were inversely associated with survival (OR 0.07; 95%CI 0.01, 0.39 and OR 0.10; 95%CI 0.01, 0.63) while higher Ang 1–7 predicted favorable outcome (OR 6.8; 95%CI 1.5, 39.9). ICU patients showed higher concentrations of all measured angiotensin metabolites, PRA-S, ALT-S and active ACE2, and lower ACE-S and AA2R than patients in the medical ward at inclusion. After seven days in the ICU, Ang I, Ang II, Ang III and Ang IV concentrations decreased, while ACE and ACE2 levels increased. Ang I, PRA-S, Ang 1–7 and Ang 1–5 concentrations correlated with the SOFA score both at the time of inclusion and after seven days, and driving pressure after seven days. Conclusions AA2R at inclusion predicted 60-day survival with moderate sensitivity, revealing a dissociation between unchanged aldosterone and increased Ang II levels in the most severely ill COVID-19 patients. After adjustment for confounders, Ang 1–7 as the final metabolite of alternative RAS was predictive for survival.https://doi.org/10.1186/s13613-025-01433-3COVID-19Acute respiratory distress syndromeRenin–angiotensin systemAldosterone |
| spellingShingle | Katharina Krenn Felix Kraft Luana Mandroiu Verena Tretter Roman Reindl-Schwaighofer Theresa Clement Oliver Domenig Matthias G. Vossen Gregor Riemann Marko Poglitsch Roman Ullrich Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study Annals of Intensive Care COVID-19 Acute respiratory distress syndrome Renin–angiotensin system Aldosterone |
| title | Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study |
| title_full | Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study |
| title_fullStr | Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study |
| title_full_unstemmed | Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study |
| title_short | Renin–angiotensin–aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study |
| title_sort | renin angiotensin aldosterone system activation in plasma as marker for prognosis in critically ill patients with covid 19 a prospective exploratory study |
| topic | COVID-19 Acute respiratory distress syndrome Renin–angiotensin system Aldosterone |
| url | https://doi.org/10.1186/s13613-025-01433-3 |
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