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BACKGROUND: Reducing hospital readmission offer potential benefits for patients, providers, payers, and policymakers to improve quality of healthcare, reduce cost, and improve patient experience. We investigated effectiveness of remdesivir in reducing 30-day coronavirus disease 2019 (COVID-19)-related readmission during the Omicron era, including older adults and those with underlying immunocompromising conditions. METHODS: This retrospective study utilized the US PINC AI Healthcare Database to identify adult patients discharged alive from an index COVID-19 hospitalization between December 2021 and February 2024. Odds of 30-day COVID-19-related readmission to the same hospital were compared between patients who received remdesivir vs those who did not, after balancing characteristics of the two groups using inverse probability of treatment weighting (IPTW). Analyses were stratified by maximum supplemental oxygen requirement during index hospitalization. RESULTS: Of 326 033 patients hospitalized for COVID-19 during study period, 210 586 patients met the eligibility criteria. Of these, 109 551 (52%) patients were treated with remdesivir. After IPTW, lower odds of 30-day COVID-19-related readmission were observed in patients who received remdesivir vs those who did not, in the overall population (3.3% vs 4.2%, respectively; odds ratio [95% confidence interval {CI}]: 0.78 [.75-.80]), elderly population (3.7% vs 4.7%, respectively; 0.78 [.75-.81]), and those with underlying immunocompromising conditions (5.3% vs 6.2%, respectively; 0.86 [.80-.92]). These results were consistent irrespective of supplemental oxygen requirements. CONCLUSIONS: Treating patients hospitalized for COVID-19 with remdesivir was associated with a significantly lower likelihood of 30-day COVID-19-related readmission across all patients discharged alive from the initial COVID-19 hospitalization, including older adults and those with underlying immunocompromising conditions.

BACKGROUND: Coronavirus disease 2019 (COVID-19) remains a major public health concern, with continued resurgences of cases and substantial risk of mortality for hospitalized patients. Remdesivir has become standard-of-care for hospitalized COVID-19 patients. Given the continued evolution of the disease, clinical management of COVID-19 relies on evidence from the current endemic period. METHODS: Using the PINC AI Healthcare Database, remdesivir effectiveness was evaluated among adults hospitalized with primary diagnosis of COVID-19 between December 2021 and February 2024. Three cohorts were analyzed: adults (≥18 years), elderly (≥65 years), and those with documented COVID-19 pneumonia. Analyses were stratified by oxygen requirements. Patients who received remdesivir were matched to those who did not receive remdesivir using propensity score matching. Cox proportional hazards models were used to examine in-hospital mortality. RESULTS: 169 965 adults hospitalized for COVID-19 were included, of whom 94 129 (55.4%) initiated remdesivir in the first 2 days of hospitalization. Remdesivir was associated with significantly lower mortality rate compared to no remdesivir among patients with no supplemental oxygen charges (adjusted HR [95% CI]: 14-day, 0.75 [.69-.82]; 28-day, 0.77 [.72-.83]) and those requiring supplemental oxygen: 14-day, 0.76 [.72-.81]; 28-day, 0.79 [.74-.83]; P < .0001 for all). Similar findings were observed for elderly patients and those hospitalized with COVID-19 pneumonia. CONCLUSIONS: This evidence builds on what has been learned from randomized controlled trials from the pandemic era to inform clinical practices. Remdesivir was associated with significant reduction in mortality for hospitalized patients including the elderly and those with COVID-19 pneumonia.

BACKGROUND: Patients with immunocompromising conditions are at increased risk for coronavirus disease 2019 (COVID-19)-related hospitalizations and deaths. Randomized clinical trials provide limited enrollment, if any, to provide information on the outcomes in such patients treated with remdesivir. METHODS: Using the US PINC AI Healthcare Database, we identified adult patients with immunocompromising conditions, hospitalized for COVID-19 between December 2021 and February 2024. The primary outcome was all-cause inpatient mortality examined in propensity score-matched patients in remdesivir vs nonremdesivir groups. Subgroup analyses were performed for patients with cancer, hematological malignancies, and solid organ or hematopoietic stem cell transplant recipients. RESULTS: Of 28 966 patients included in the study, 16 730 (58%) received remdesivir during the first 2 days of hospitalization. After propensity score matching, 8822 patients in the remdesivir and 8822 patients in the nonremdesivir group were analyzed. Remdesivir was associated with a significantly lower mortality rate among patients with no supplemental oxygen (adjusted hazard ratio [95% confidence interval], 0.73 [.62-.86] at 14 days and 0.79 [.68-.91] at 28 days) and among those with supplemental oxygen (0.75 [.67-.85] and 0.78 [.70-.86], respectively). Remdesivir was also associated with lower mortality rates in subgroups of patients with cancer, hematological malignancies (leukemia, lymphoma, or multiple myeloma), and solid organ or hematopoietic stem cell transplants. CONCLUSIONS: In this large cohort of patients with immunocompromising conditions hospitalized for COVID-19, remdesivir was associated with significant improvement in survival, including patients with varied underlying immunocompromising conditions. The integration of current real-world evidence into clinical guideline recommendations can inform clinical communities to optimize treatment decisions in the evolving COVID-19 era, extending beyond the conclusion of the public health emergency declaration.

BACKGROUND: Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. METHODS: In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. RESULTS: Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P = .61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function. CONCLUSIONS: Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment. CLINICAL TRIALS REGISTRATION: EudraCT 2020-005416-22; Clinical Trials.gov NCT04745351.

Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1-O-octadecyl-2-O-benzyl-sn-glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its in vivo efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the in vitro broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043. Here, we demonstrate that V2043, V2053, and V2067 are all orally bioavailable, well-tolerated, and achieve high sustained plasma levels after single oral daily dosing. All three phospholipid prodrugs are significantly more active than RVn in vitro and significantly reduce SARS-CoV-2 lung titers in prophylaxis and treatment mouse models of SARS-CoV-2 B.1.351 infection. On a molar basis, V2043 and V2067 are substantially more active than obeldesivir/GS-5245 and molnupiravir in vivo. Together, these data support the continued development of phospholipid RVn prodrugs for the treatment of SARS-CoV-2 and other RNA viruses of clinical concern.

BACKGROUND: Although antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter Adaptive COVID-19 Treatment Trial 1, which randomized patients to remdesivir or placebo. METHODS: Longitudinal specimens collected during hospitalization from a substudy of 642 patients with COVID-19 were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed. RESULTS: Higher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95% CI, 1.40-2.71) for levels >245 pg/mL vs 1.04 (95% CI, .76-1.42) for levels

Aim: This observational study investigated the association between remdesivir treatment during hospitalization for COVID-19 and 30-day COVID-19-related and all-cause readmission across different variants time periods. Patients & methods: Hospitalization records for adult patients discharged from a COVID-19 hospitalization between 1 May 2020 to 30 April 2022 were extracted from the US PINC AI Healthcare Database. Likelihood of 30-day readmission was compared among remdesivir-treated and nonremdesivir-treated patients using multivariable logistic regression models adjusted for age, corticosteroid treatment, Charlson comorbidity index and intensive care unit stay during the COVID-19 hospitalization. Analyses were stratified by maximum supplemental oxygen requirement and variant time period (pre-Delta, Delta and Omicron). Results: Of the 440,601 patients discharged alive after a COVID-19 hospitalization, 248,785 (56.5%) patients received remdesivir. Overall, remdesivir patients had a 30-day COVID-19-related readmission rate of 3.0% and all-cause readmission rate of 6.3% compared with 5.4% and 9.1%, respectively, for patients who did not receive remdesivir during their COVID-19 hospitalization. After adjusting for demographics and clinical characteristics, remdesivir treatment was associated with significantly lower odds of 30-day COVID-19-related readmission (odds ratio 0.60 [95% confidence interval: 0.58-0.62]), and all-cause readmission (0.73 [0.72-0.75]). Significantly lower odds of 30-day readmission in remdesivir-treated patients was observed across all variant time periods. Conclusion: Treating patients hospitalized for COVID-19 with remdesivir is associated with a statistically significant reduction in 30-day COVID-19-related and all-cause readmission across variant time periods. These findings indicate that the clinical benefit of remdesivir may extend beyond the COVID-19 hospitalization.

Background: The effectiveness of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal insufficiency remains underexplored. Objectives: To evaluate whether remdesivir reduces the risk of mortality or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) in this population. Methods: This retrospective observational study utilising the COVID-19 Registry Japan (COVIREGI-JP) included noncritical patients with COVID-19 and severe renal insufficiency (defined as serum creatinine levels ≥3 mg/dL, on maintenance dialysis, or kidney transplant recipients) admitted to Japanese hospitals within 7 days of symptom onset between January 1, 2020 and May 8, 2023. Patients were classified into the remdesivir group if remdesivir was initiated within the first 2 days of admission. We estimated the multivariable-adjusted hazard ratio (HR) for mortality and initiation of IMV/ECMO using landmark analysis to address immortal time bias. Results: Among the 1,449 patients included in the landmark analysis (median age, 74 years [interquartile range 62–84 years]; 992 [68.5%] were male), 272 initiated remdesivir within the first 2 days of admission. During the 28 days from the landmark timepoint, 19 (7.0%) and 136 (11.6%) patients in the remdesivir and control groups, respectively, had an outcome. The remdesivir group had a lower risk of mortality or IMV/ECMO initiation than the control group (adjusted HR, 0.44; 95% confidence interval, 0.23–0.83). Conclusions: In noncritical patients with COVID-19 and severe renal insufficiency at admission, initiating remdesivir early after disease onset, within the first 2 days of admission, led to a lower risk of mortality or IMV/ECMO initiation, compared with non-initiation of remdesivir. [ABSTRACT FROM AUTHOR]

Remdesivir (RDV) is a drug that exhibits broad-spectrum antiviral against RNA viruses, and so this drug could be an appropriate therapeutic candidate. To increase the therapeutic efficiency of Remdesivir, nanoparticles are employed to prolong bioavailability and facilitate targeted delivery in the body and the drug transportation. In this study, we employed classical atomistic molecular dynamics simulations to characterize the adsorption properties of this compound on Ag nanoparticles. The simulation results show that Remdesivir molecules adsorb onto the surface of Ag nanoparticles in a size-dependent manner, so that smaller AgNPs exhibit a higher degree of Remdesivir coating than larger ones. The results also show that the coating of Remdesivir molecules on nanoparticles can improve their pharmacokinetic properties in vivo studies. These findings provide a basis for designing nanoparticle-based drug delivery systems. [ABSTRACT FROM AUTHOR]

Background: COVID-19 remains a complex health challenge. We analysed the characteristics and outcomes of COVID-19-related hospitalisations during JN.1 variant dominance. Methods: Conducted in a hospital serving a socioeconomically deprived population, this study included all adults hospitalised with COVID-19 from 1st November 2023 to 31st August 2024. The primary outcome was in-hospital mortality, analysed in relation to demographic, clinical, and laboratory parameters. Results: Among 122 individuals (median age 76 years, 58.2% males, median comorbidity index 5), 114/122 (93.4%) had received ≥ 1 SARS-CoV-2 vaccination, with a median of 23 months elapsed since the last dose. Fever (67/122, 54.9%) and dyspnoea (49/122, 40.2%) were common presenting symptoms, with 78/122 (64%) showing CT evidence of SARS-CoV-2 pneumonia; 25/122 (20%) had purely neurological presentations. Treatment included remdesivir (115/122, 94.3%) and/or nirmatrelvir/ritonavir (9/122, 7.4%), sotrovimab (15/122, 12.3%), corticosteroids (61/122, 50.0%), and oxygen supplementation (76/122, 62.3%). Whereas 107/122 (87.7%) were discharged after a median of seven days, in-hospital mortality was 15/122 (12.3%) after a median of 16 days. Baseline factors associated with mortality were neutrophil-lymphocyte ratio > 8, D-dimer ≥ 1800 ng/mL, procalcitonin ≥ 1.0 ng/mL, and albumin < 3.2 g/dL; during admission, nasopharyngeal SARS-CoV-2 antigen positivity persisting for > 12 days, hospitalisation for ≥ 10 days, higher oxygen requirements with the resulting corticosteroid use, and healthcare-associated bacteraemia were associated with increased odds of mortality. Conclusions: Baseline laboratory parameters and persistent SARS-CoV-2 antigen positivity despite antiviral therapy offer readily available prognostic insights for patients hospitalised with COVID-19. It is imperative to advocate for up-to-date COVID-19 vaccination among older people and other vulnerable groups. [ABSTRACT FROM AUTHOR]

Background: Remdesivir is recommended to treat hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is known to affect glucose metabolism in individuals with and without diabetes. However, little is known about the possibility of hypoglycemia associated with remdesivir. Our case is the first report demonstrating the development of severe hypoglycemia following remdesivir treatment in an elderly man without diabetes. Case presentation: A 73-year-old man developed COVID-19 following surgery for sigmoid volvulus. The patient's medical history included surgery for posterior correction of scoliosis, Chiari malformation type I, and syringomyelia. There was no history of diabetes mellitus. The patient was started on remdesivir (200 mg on day 1, followed by 100 mg intravenously daily until day 9). On day 7, following remdesivir administration, the patient developed severe hypoglycemia with a blood glucose (BG) level of 25 mg/dL. On day 8 and 9 he repeatedly developed severe hypoglycemia following administration of remdesivir. Considering the timing of administration, the patient's hypoglycemia could have been caused by remdesivir. Therefore, his treatment with remdesivir was discontinued. After discontinuation, his BG levels normalized. The Naranjo algorithm, a tool for evaluating the causality of adverse drug reactions, classified the event as "Probable" (6 points). Conclusions: Remdesivir may have caused hypoglycemia in this case. Health care professionals should be aware of its potential effects on glucose metabolism and the risk of hypoglycemia when treating patients with remdesivir. [ABSTRACT FROM AUTHOR]

Background: Post-COVID condition (PCC) is characterized by persisting symptoms after the resolution of acute COVID-19. Remdesivir (RDV), a broad-spectrum antiviral drug, has been widely used in patients hospitalized with COVID-19 requiring oxygen therapy. We aimed to evaluate the effects of RDV on PCC by assessing patient-reported and functional outcomes. Methods: We used the data from a single-center registry, including formerly hospitalized post-COVID patients (N = 293). Propensity score matching (PSM) was used (16 criteria, 1:1 ratio) to obtain two comparable groups: those who received standard-of-care (SOC, N = 94) and those treated with RDV in addition to SOC (SOC + RDV, N = 94). Primary outcomes were asymptomatic status and at least 50% symptom score reduction at post-COVID follow-up. Secondary outcomes included results of pulmonary function (PF) tests, 6-minute walk test (6MWT), and quality-of-life (QoL) questionnaires. Results: After PSM, baseline patient characteristics showed no significant differences between the two groups. Most patients were still symptomatic (60% vs. 66%). In the SOC + RDV group, the use of oxygen supplementation (94 vs. 80%, p = 0.005) and steroids (97 vs. 88%, p = 0.027) during infection were higher, while patients presented at their post-COVID visits earlier (median 68 vs. 97 days, p = 0.003). Complete or at least 50% symptom resolution were reported at a significantly earlier stage after infection in the SOC + RDV group compared to the SOC group (multivariable-adjusted HR = 2.28, 95% CI = 1.33–3.92, p = 0.003; and HR = 2.08, 95% CI = 1.43–3.02, p < 0.001; respectively). In the SOC + RDV group, fewer patients experienced sleep disturbances at PCC, and sleep-related questionnaires (Pittsburg Sleep Quality Index, PSQI) results showed significantly better sleep quality (14 vs. 27% and 5.9 vs. 7.7 points, respectively). There were no notable differences in results of PF tests, 6MWT, and other QoL questionnaires. Conclusion: In this propensity score matched cohort, the use of RDV was associated with earlier patient reported symptom resolution during the PCC period, while there were no notable differences in functional outcomes. Our results indicate a possible beneficial effect of RDV in terms of faster symptom resolution after COVID19 infection. [ABSTRACT FROM AUTHOR]

Remdesivir and moxifloxacin hydrochloride are among the most frequently co-administered drugs used for COVID-19 treatment. The current work aims to evaluate green spectrophotometric methodologies for estimating remdesivir and moxifloxacin hydrochloride in different matrices for the first time. The proposed approaches were absorbance subtraction, extended ratio subtraction and amplitude modulation methods. In order to determine the absorbance of the investigated medications in combination at the isoabsorptive point, the pure moxifloxacin hydrochloride absorbance factor is applied using the absorbance subtraction method, which modifies the zero absorption spectra of the drugs under investigation at the isoabsorptive point (229 nm). The spectrum of moxifloxacin hydrochloride is more extended in the plateau area between 340 and 400 nm, where remdesivir exhibits no absorption. So, also, the ratio spectra were successfully manipulated for quantification of the two drugs. Regarding the pharmacokinetic profile of remdesivir (Cmax 4420 ng/mL) and moxifloxacin hydrochloride (Cmax 3.56 µg/mL), the proposed methods were effectively used to spectrophotometrically determine remdesivir and moxifloxacin hydrochloride in plasma matrix. The new approach was validated using the ICH guidelines for specificity, linearity, precision, and accuracy. The greenness of the reported methodologies was evaluated using two metrics: the analytical eco-scale and the green analytical procedure index. [ABSTRACT FROM AUTHOR]

Co-administration of COVID-19 RNA polymerase inhibitors, remdesivir and favipiravir, has synergistic benefits. Together they reduce viral load and inflammation more effectively than either drug used alone. Corticosteroids like dexamethasone are used alongside antivirals in multidrug combination regimens. A new HPTLC method was utilized to isolate and quantitatively determine the three medicines of the COVID-19 therapeutic protocol, remdesivir, favipiravir and dexamethasone, using the anticoagulant apixaban as an internal standard in human plasma. The mobile phase system used a solvent mixture of ethyl acetate, hexane, and acetic acid (9:1:0.3, by volume). At 254 nm, well-resolved spots with Rf values of 0.3 for remdesivir, 0.64 for dexamethasone, and 0.77 for favipiravir have been observed. To ensure compliance with FDA regulations, a validation study was conducted. Quantitation limits as low as 0.1 µg/band have been achieved with remdesivir and dexamethasone, and 0.2 µg/band with favipiravir, demonstrating excellent sensitivities. From 97.07% to 102.77%, the drugs were recovered from human plasma that had been artificially spiked. The whiteness of the method has been assessed using RGB 12 algorithm and a percentage of whiteness of 95.6% has been obtained. [ABSTRACT FROM AUTHOR]

Background Treatment guidelines were developed early in the pandemic when much about coronavirus disease 2019 (COVID-19) was unknown. Given the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), real-world data can provide clinicians with updated information. The objective of this analysis was to assess mortality risk in patients hospitalized for COVID-19 during the Omicron period receiving remdesivir + dexamethasone versus dexamethasone alone. Methods A large, multicenter US hospital database was used to identify adult patients hospitalized with a primary discharge diagnosis of COVID-19 flagged as "present-on-admission" and treated with remdesivir + dexamethasone or dexamethasone alone between December 2021 and April 2023. Patients were matched using 1:1 propensity score matching and stratified by baseline oxygen requirements. Cox proportional hazards model was used to assess time to 14- and 28-day in-hospital all-cause mortality. Results A total of 33 037 patients were matched, with most patients ≥65 years old (72%), White (78%), and non-Hispanic (84%). Remdesivir + dexamethasone was associated with lower mortality risk versus dexamethasone alone across all baseline oxygen requirements at 14-days (no supplemental oxygen charges: adjusted hazard ratio [95% confidence interval {CI}]: 0.79 [.72–.87], low flow oxygen: 0.70 [.64–.77], high flow oxygen/non-invasive ventilation: 0.69 [.62–.76], invasive mechanical ventilation/extracorporeal membrane oxygen (IMV/ECMO): 0.78 [.64–.94]), with similar results at 28-days. Conclusions Remdesivir + dexamethasone was associated with a significant reduction in 14- and 28-day mortality compared to dexamethasone alone in patients hospitalized for COVID-19 across all levels of baseline respiratory support, including IMV/ECMO. However, the use of remdesivir + dexamethasone still has low clinical practice uptake. In addition, these data suggest a need to update the existing guidelines. [ABSTRACT FROM AUTHOR]

Background and Objective: Remdesivir is a nucleotide analog prodrug approved for the treatment of COVID-19. This study evaluated the pharmacokinetics and safety of remdesivir and its metabolites (GS-704277 and GS-441524) in participants with varying degrees of renal impairment. Results of this phase I study, along with those of a phase III study, contributed to an extension of indication for remdesivir in the USA and Europe for use in patients with COVID-19 with all stages of renal impairment, including those on dialysis, with no dose adjustment. Methods: This phase I, open-label, parallel-group study enrolled participants who had mild (n = 12), moderate (n = 11), or severe (n = 10) renal impairment or kidney failure (n = 6 with dialysis, n = 4 without dialysis). Healthy matched controls were enrolled as reference. Remdesivir was given as single intravenous doses of 100 mg (mild and moderate renal impairment), 40 mg (severe renal impairment, kidney failure predialysis), and 20 mg (kidney failure postdialysis and without dialysis). Results: Plasma pharmacokinetics of remdesivir were not affected by mild, moderate, or severe renal impairment or kidney failure. Geometric least squares mean ratios ranged from 0.8 to 1.2 for remdesivir area under the plasma concentration–time curve (AUC). GS-704277 AUC was up to 2.8-fold higher and GS-441524 AUC up to 7.9-fold higher in participants with renal impairment. Adverse events and laboratory abnormalities were consistent with the existing safety profile for remdesivir. Conclusions: Observed pharmacokinetics for remdesivir and its metabolites in participants with renal impairment aligned with expected changes based on known routes of elimination. Remdesivir was generally safe and well tolerated in participants with renal impairment, and no new safety concerns were identified. These results, along with those from the phase III study in patients with COVID-19 with severely reduced kidney function, support the use of remdesivir in patients with any degree of renal impairment with no dose adjustments. Trial Registration: EudraCT no. 2020-003441-10; 9 July 2020. [ABSTRACT FROM AUTHOR]

Background As coronavirus disease 2019 (COVID-19)–related mortality remains a concern, optimal management of patients hospitalized for COVID-19 continues to evolve. We developed a population model based on real-world evidence to quantify the clinical impact of increased utilization of remdesivir, the effectiveness of which has been well established in hospitalized patients with COVID-19. Methods The PINC AI healthcare database records for patients hospitalized for COVID-19 from January to December 2023 were stratified by those treated with or without remdesivir ("RDV" and "no RDV") and by supplemental oxygen requirements: no supplemental oxygen charges (NSOc), low-flow oxygen (LFO), and high-flow oxygen/non-invasive ventilation. Key vulnerable subgroups such as elderly and immunocompromised patients were also evaluated. The model applied previously published hazard ratios (HRs) to 28-day in-hospital mortality incidence to determine the number of potential lives saved if additional no RDV patients had been treated with remdesivir upon hospital admission. Results Of 84 810 hospitalizations for COVID-19 in 2023, 13,233 no RDV patients were similar in terms of characteristics and clinical presentation to the RDV patients. The model predicted that initiation of remdesivir in these patients could have saved 231 lives. Projected nationally, this translates to >800 potential lives saved (95% confidence interval, 469–1126). Eighty-nine percent of potential lives saved were elderly and 19% were immunocompromised individuals. Seventy-six percent were among NSOc or LFO patients. Conclusions This public health model underscores the value of initiating remdesivir upon admission in patients hospitalized for COVID-19, in accordance with evidence-based best practices, to minimize lives lost because of severe acute respiratory syndrome coronavirus 2 infection. [ABSTRACT FROM AUTHOR]

The article focuses on the effectiveness of remdesivir for hospitalized COVID-19 patients during the Omicron era, based on cohort studies. Topics include the challenges of conducting clinical trials during a global pandemic, the outcomes of previous randomized trials on remdesivir, and evidence from real-world cohort studies regarding its impact on patient recovery.

The first Adaptive COVID‐19 Treatment Trial (ACTT‐1) showed that remdesivir improved COVID‐19 recovery time compared with placebo in hospitalized adults. The secondary outcome of mortality was almost significant overall (p = 0.07) and highly significant for people receiving supplemental oxygen at enrollment (p = 0.002), suggesting a mortality benefit concentrated in this group. We explore analysis methods that are helpful when a single subgroup benefits from treatment and apply them to ACTT‐1, using baseline oxygen use to define subgroups. We consider two questions: (1) is the remdesivir effect for people receiving supplemental oxygen real, and (2) does this effect differ from the overall effect? For Question 1, we apply a Bonferroni adjustment to subgroup‐specific hypothesis tests and the Westfall and Young permutation test, which is valid when small cell counts preclude normally distributed test statistics (a frequently unexamined condition in subgroup analyses). For Question 2, we introduce Qmax, the largest standardized difference between subgroup‐specific effects and the overall effect. Qmax simultaneously tests whether any subgroup effect differs from the overall effect and identifies the subgroup benefitting most. We demonstrate that Qmax strongly controls the familywise error rate (FWER) when test statistics are normally distributed with no mean–variance relationship. We compare Qmax to a related permutation test, SEAMOS, which was previously proposed but not extensively applied or tested. We show that SEAMOS can have inflated Type 1 error under the global null when control arm event rates differ between subgroups. Our results support a mortality benefit from remdesivir in people receiving supplemental oxygen. [ABSTRACT FROM AUTHOR]

Background: There is little information about the risk of drug-induced QT prolongation by remdesivir as the most important FDA approved anti COVID-19 drug. Prolongation of corrected QT interval (QTc) is considered as an indicator of an unfavorable outcome which may ultimately induce torsade de pointes and provoke ventricular fibrillation. The aim of this study was to determine the effects of remdesivir on QTc in patients with severe COVID 19 disease. Methods: A historical cohort study was conducted on 249 patients who experienced severe COVID-19 disease and were candidate for treatment by intravenous remdesivir. We obtained a 12 lead electrocardiogram at the admission time and five days later to find any significant change in QTc and QT interval following therapy. We took blood samples at the time of hospitalization and then every day to determine the serum levels of electrolytes, complete blood count, fasting blood sugar (FBS), creatinine (Cr), and complete blood count. Results: The results of this analysis showed blood pressure and heart rate (HR) were lower and total white blood cells and neutrophil counts, FBS and Cr levels were higher at fifth day than first day of study (P value < 0.001). Furthermore, QT interval was more prolonged at fifth day compared with beginning of remdesivir therapy (379.51 ± 34.90ms vs. 366.72 ± 30.97ms, P value < 0.001). However, QTc was not significantly increased at fifth day in comparison with first day (402.37 ± 33.62ms vs. 400.76 ± 30.18ms, P value = 0.524 by Bazett's formula and 402.81 ± 36.33 vs. 400.78 ± 32.49, P value = 0.459 by Fridericia's formula). Conclusions: The current study found no evidence linking the administration of remdesivir with prolongation of the QTc interval. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is considered an infectious disease which is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neonatal COVID-19 had been occurred in many countries which would indicate the need of effective and safe treatment for these vulnerable group. In this study, we showed symptoms of corona virus in neonates, investigation of coronavirus in neonates and radiological features of neonatal COVID-19. In addition, we discussed management of neonates with COVI-19, antiviral treatment, monoclonal antibodies administration, immunomodulatory therapy, antibiotics, vitamins, and minerals in the treatment of neonatal COVID-19, and also telemedicine in neonatal COVID-19 and feeding the newborn of COVID-19 mother. We also discussed multisystem inflammatory syndrome in neonates (MIS-N), management of affected COVID-19 neonates and discussion of the complication of the neonatal COVID-19. We further discussed the methods of dealing with COVID-19 neonates and the research done on the neonatal COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical–pathological changes associated with EBOV disease in this model. [ABSTRACT FROM AUTHOR]

Favipiravir (FVP) and remdesivir (RDV) have demonstrable antiviral activity against SARS-CoV-2. Here, the efficacy of FVP, RDV, and FVP with RDV (FVP + RDV) in combination was assessed in Syrian golden hamsters challenged with SARS-CoV- 2 (B.1.1.7) following intraperitoneal administration. At day 4 post infection, viral RNA and viral antigen expression were significantly lower in lungs for all three treatment groups compared to the sham treatment. Similarly, viral titres in the lungs were lower in all treatment groups compared to the sham treatment. The FVP + RDV combination was the only treatment group where viral RNA in nasal turbinate and lung, virus titres in lung, and viral antigen expression (lung) were all lower than those for the sham treatment group. Moreover, lower viral titre values were observed in the FVP + RDV group compared to other treatment groups, albeit only significantly lower in comparison to those in the RDV-only-treated group. Further assessment of the potential utility of FVP in combination with RDV may be warranted. Future studies should also consider whether the combination of these two drugs may reduce the speed at which drug resistance mutations are selected. [ABSTRACT FROM AUTHOR]

The number of studies and reviews conducted for the Carboxylesterase gene is limited in comparison with other enzymes. Carboxylesterase (CES) gene or human carboxylesterases (hCES) is a multigene protein belonging to the α/β-hydrolase family. Over the last decade, two major carboxylesterases (CES1 and CES2), located at 16q13–q22.1 on human chromosome 16 have been extensively studied as important mediators in the metabolism of a wide range of substrates. hCES1 is the most widely expressed enzyme in humans, and it is found in the liver. In this review, details regarding CES1 substrates include both inducers (e.g. Rifampicin) and inhibitors (e.g. Enalapril, Diltiazem, Simvastatin) and different types of hCES1 polymorphisms (nsSNPs) such as rs2244613 and rs71647871. along with their effects on various CES1 substrates were documented. Few instances where the presence of nsSNPs exerted a positive influence on certain substrates which are hydrolyzed via hCES1, such as anti-platelets like Clopidogrel when co-administered with other medications such as angiotensin-converting enzyme (ACE) inhibitors were also recorded. Remdesivir, an ester prodrug is widely used for the treatment of COVID-19, being a CES substrate, it is a potent inhibitor of CES2 and is hydrolyzed via CES1. The details provided in this review could give a clear-cut idea or information that could be used for further studies regarding the safety and efficacy of CES1 substrate. [ABSTRACT FROM AUTHOR]

During the early days of the COVID-19 pandemic, low dose radiation therapy (LDRT) was proposed as a potentially effective treatment method. To minimize potential toxicity, the initial treatment approach involved a few mGy of adapting radiation followed by a single 250 mGy whole lung challenging dose. However, antiviral drugs were also introduced as a promising treatment option, which were thought to have the potential to revolutionize the management of the crisis. Despite early warnings, many physicians did not fully consider the key point that, in contrast with LDRT, antiviral drug treatments can result in strong selective pressure on the virus. This can lead to the emergence of new SARS-CoV-2 variants, a phenomenon that can have serious global consequences. After more than two years, the truth has been revealed: the WHO Guideline Development Group has advised against the use of remdesivir, a widely used antiviral medication, for COVID-19. Meanwhile, a growing body of evidence suggests that LDRT can be a promising, low-risk approach for avoiding or delaying invasive respiratory support in COVID-19 patients. Although there is substantial supporting documentation, more highquality, controlled, and randomized double-blind clinical trials are needed to further investigate the efficacy and potential therapeutic mechanisms of LDRT for COVID-19. [ABSTRACT FROM AUTHOR]