A Meta-Analysis of Association between Remdesivir and Mortality among Critically-Ill COVID-19 Patients

Cho

et al. 2022

Korean J Intern Med

Background/Aims: The risk factors and clinical impacts of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remain controversial, and no data have been reported in Korea. This study aimed to investigate the epidemiology and importance of CAPA diagnostic efforts and to identify the predictors of CAPA and the impacts on clinical outcomes.Methods: Between January 2020 and May 2021, data of severely to critically ill COVID-19 patients were extracted from seven hospitals of the Catholic Medical Center through a clinical data warehouse. Corticosteroid use was subcategorized into total cumulative dose, early 7-day dose, mean daily dose, and duration of use.Results: A total of 2,427 patients were screened, and 218 patients were included. CAPA was diagnosed in 4.6% (10/218) of all hospitalized and 11.2% (10/89) of intensive care unit patients. Total cumulative dose (over 1,000 mg as methylprednisolone) and daily high-dose corticosteroid use (over 60 mg/day) were independent predictors but not early 7-day high-dose corticosteroid use (over 420 mg/week) (odds ratio [OR], 1.731; 95% confidence interval [CI], 0.350 to 8.571) nor prolonged use (OR, 2.794; 95% CI, 0.635 to 13.928). In-hospital overall mortality was 11.9% (26 of 218). CAPA itself did not affect the outcome; rather, daily high-dose steroid use significantly increased the 30-day mortality (hazard ratio, 5.645; 95% CI, 1.225 to 26.091).Conclusions: CAPA was not uncommon, especially in critically ill patients. Daily high-dose corticosteroid use was the predictor of CAPA and associated with high mortality rates. High-dose corticosteroids use after early inflammatory phase should be avoided, and active surveillance methods for CAPA are essential for those high-risk patients.

Section: Discussionmentioning

confidence: 99%

Risk factors and clinical impact of COVID-19-associated pulmonary aspergillosis: Multicenter retrospective cohort study

Cho

et al. 2022

Korean J Intern Med

“…As the COVID-19 pandemic continues, several drugs have been researched and developed to treat COVID-19 [ 4 5 6 7 8 ]. In Korea, previous studies examined the effectiveness of the treatment for Korean patients, and guidelines for the treatment have been published and updated [ 15 16 17 18 ]. Nirmatrelvir/ritonavir was the first oral antiviral agent approved by the US Food and Drug Administration and was the first oral antiviral agent used in Korea [ 8 10 ].…”

Section: Discussionmentioning

confidence: 99%

Nirmatrelvir/Ritonavir Prescription Rate and Outcomes in Coronavirus Disease 2019: A Single Center Study

et al. 2022

Background Nirmatrelvir/ritonavir was Korea's first oral antiviral agent to treat coronavirus disease 2019 (COVID-19). We analyzed the nirmatrelvir/ritonavir prescription rate and treatment outcomes in treatment-eligible patients with COVID-19 receiving home-based care. Materials and Methods We retrospectively collected data of patients with COVID-19-eligible for nirmatrelvir/ritonavir treatment from January 14, 2022, to February 15, 2022. We analyzed the prescription rate of nirmatrelvir/ritonavir, the reasons for non-prescription, and patient outcomes. Results A total of 414 patients were included, of whom 44.2% were male, and the mean age was 64.6 (standard deviation [SD] = 8.5). Approximately 73.2% (n = 303) of patients were not prescribed nirmatrelvir/ritonavir. More than fourth-fifths of the patients refused nirmatrelvir/ritonavir treatment (n = 262, 86.5%). The mean symptom duration was significantly shorter in the prescription group (5.2 days [SD = 2.3] vs. 4.4 days [SD = 1.9], P = 0.001). A total of 6 (1.4%) patients were hospitalized, and none of the patients who received nirmatrelvir/ritonavir required admission. Among the patients prescribed nirmatrelvir/ritonavir (n = 111), 17 (15.3%) patients experienced side effects, and 5 (4.5%) patients discontinued nirmatrelvir/ritonavir due to side effects. Conclusion The nirmatrelvir/ritonavir prescription rate was low, with more than fourth-fifths of non-prescriptions being due to patient refusal. Symptom resolution was faster, and no life-threatening side effects were reported. Accurate information about drug safety must be provided to patients to make informed decisions regarding nirmatrelvir/ritonavir treatment.

“…In the light of upcoming approaches to orally deliver the remdesivir nucleoside GS-441524 or other pro-drugs with higher oral bioavailability (Li et al 2021 ; Lo et al 2021 ; Schäfer et al 2022 , 2021 ; Xie and Wang 2021 ) or to administrate remdesivir in earlier stages of COVID-19 to elevate its antiviral efficacy (EMA 2021a ; FDA 2022 ; Gottlieb et al 2022 ; Paranjape et al 2021 ; Razzack et al 2021 ), our results argue for a careful surveillance of cardiac function during therapy.…”

Section: Discussionmentioning

confidence: 99%

The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro

et al. 2022

Remdesivir is a prodrug of a nucleoside analog and the first antiviral therapeutic approved for coronavirus disease. Recent cardiac safety concerns and reports on remdesivir-related acute kidney injury call for a better characterization of remdesivir toxicity and understanding of the underlying mechanisms. Here, we performed an in vitro toxicity assessment of remdesivir around clinically relevant concentrations (Cmax 9 µM) using H9c2 rat cardiomyoblasts, neonatal mouse cardiomyocytes (NMCM), rat NRK-52E and human RPTEC/TERT1 cells as cell models for the assessment of cardiotoxicity or nephrotoxicity, respectively. Due to the known potential of nucleoside analogs for the induction of mitochondrial toxicity, we assessed mitochondrial function in response to remdesivir treatment, early proteomic changes in NMCM and RPTEC/TERT1 cells and the contractile function of NMCM. Short-term treatments (24 h) of H9c2 and NRK-52E cells with remdesivir adversely affected cell viability by inhibition of proliferation as determined by significantly decreased 3H-thymidine uptake. Mitochondrial toxicity of remdesivir (1.6–3.1 µM) in cardiac cells was evident by a significant decrease in oxygen consumption, a collapse of mitochondrial membrane potential and an increase in lactate secretion after a 24–48-h treatment. This was supported by early proteomic changes of respiratory chain proteins and intermediate filaments that are typically involved in mitochondrial reorganization. Functionally, an impedance-based analysis showed that remdesivir (6.25 µM) affected the beat rate and contractility of NMCM. In conclusion, we identified adverse effects of remdesivir in cardiac and kidney cells at clinically relevant concentrations, suggesting a careful evaluation of therapeutic use in patients at risk for cardiovascular or kidney disease.