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      Remdesivir, dexamethasone and angiotensin-converting enzyme inhibitors use and mortality outcomes in COVID-19 patients with concomitant troponin elevation

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          Abstract

          BACKGROUND

          There are indications that viral myocarditis, demand ischemia, and renin-angiotensin-aldosterone system pathway activation play essential roles in troponin elevation in coronavirus disease 2019 (COVID-19) patients. Antiviral medications and steroids are used to treat viral myocarditis, but their effect in patients with elevated troponin, possibly from myocarditis, has not been studied.

          AIM

          To evaluate the effect of dexamethasone, remdesivir, and angiotensin-converting enzyme (ACE) inhibitors (ACEI) on mortality in COVID-19 patients with elevated troponin.

          METHODS

          Our retrospective observational study involved 1788 COVID-19 patients at seven hospitals in Southern California, United States. We did a backward selection Cox multivariate regression analysis to determine predictors of mortality in our study population. Additionally, we did a Kaplan Meier survival analysis in the subset of patients with elevated troponin, comparing survival in patients that received dexamethasone, remdesivir, and ACEI with those that did not.

          RESULTS

          The mean age was 66 years (range 20-110), troponin elevation was noted in 11.5% of the patients, and 29.9% expired. The patients' age [hazard ratio (HR) = 1.02, P < 0.001], intensive care unit admission (HR = 5.07, P < 0.001), and ventilator use (HR = 0.68, P = 0.02) were significantly associated with mortality. In the subset of patients with elevated troponin, there was no statistically significant difference in survival in those that received remdesivir (0.07), dexamethasone ( P = 0.63), or ACEI ( P = 0.8) and those that did not.

          CONCLUSION

          Although elevated troponin in COVID-19 patients has been associated with viral myocarditis and ACE II receptors, conventional viral myocarditis treatment, including antiviral and steroids, and ACEI did not show any effect on mortality in these patients.

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          Most cited references30

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          Remdesivir for the Treatment of Covid-19 — Final Report

          Abstract Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Conclusions Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)
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            A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury

            During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world 1,2,3 . A new coronavirus (SARS-CoV) was identified as the SARS pathogen 4,5,6,7 , which triggered severe pneumonia and acute, often lethal, lung failure 8 . Moreover, among infected individuals influenza such as the Spanish flu 9,10 and the emergence of new respiratory disease viruses 11,12 have caused high lethality resulting from acute lung failure 13 . In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor 14 . The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses. Supplementary information The online version of this article (doi:10.1038/nm1267) contains supplementary material, which is available to authorized users.
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              Third universal definition of myocardial infarction.

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                Author and article information

                Contributors
                Journal
                World J Cardiol
                WJC
                World Journal of Cardiology
                Baishideng Publishing Group Inc
                1949-8462
                26 September 2023
                26 September 2023
                : 15
                : 9
                : 427-438
                Affiliations
                Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
                Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States. heathermaoz@ 123456gmail.com
                Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
                Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
                Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
                Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
                Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
                Author notes

                Author contributions: Umeh CA, Maoz H, Obi J, Dakoria R, Patel S, Maity G and Barve P conceptualized and revised the study design; Umeh CA analyzed the data; Maoz H, Umeh CA, Obi J, Dakoria R, Patel S, and Maity G, wrote the first draft of the paper; Barve P and Umeh CA, reviewed and revised the paper; Maoz H led and coordinated the research and writing of the manuscript; Barve P and Umeh CA supervised the project; all authors have read and approved the final manuscript.

                Corresponding author: Heather Maoz, MD, Doctor, Internal Medicine, Hemet Global Medical Center, 1117 E. Devonshire Ave., Hemet, CA 92543, United States. heathermaoz@ 123456gmail.com

                Article
                jWJC.v15.i9.pg427 85096
                10.4330/wjc.v15.i9.427
                10600781
                cb38e441-9e33-4862-bc66-be9b759719f4
                ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 21 April 2023
                : 12 July 2023
                : 17 August 2023
                Categories
                Retrospective Study

                coronavirus disease 2019,troponin elevation,remdesevir,ace inhibitor,steroids

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