Remdesivir Treatment Research Articles

Reply to Boyd et al., "Evidence that remdesivir treatment reduces viral titers in patients with COVID-19".

Reply to Boyd et al., "Evidence that remdesivir treatment reduces viral titers in patients with COVID-19".

Integrated Analysis of Remdesivir and Paxlovid in COVID-19 Patients: A Personalized Approach to High-Risk Individuals for Severe Evolution

Background/Objectives: COVID-19 led to a pandemic that has brought misery to millions of people but more so to those with pre-existing conditions. For this infection, several antiviral drugs were employed, including remdesivir (R) and Paxlovid (nirmatrelvir/ritonavir (NR)). Methods: The current study compared the effectiveness of remdesivir and Paxlovid treatment for COVID-19 patients with comorbid conditions. Data from a cohort of 151 adult patients with COVID-19 who also had associated comorbidities were used in this study. These patients were treated with antivirals according to local guidelines. The subjects included 78 case-patients assigned to group R and 73 to group NR. Results: In group NR, a considerable improvement in oxygen saturation was seen in the first 24 h of treatment (p = 0.010), but the levels were significantly higher from the second day of treatment (p < 0.001) in group R of patients. At the end of the 5 days of treatment, the oxygen saturation improved statistically significantly compared to the admission day, but only in the R group (95.11 ± 1.80; 91.76 ± 1.80; p < 0.001). Conclusions: Both drugs can be considered a breakthrough in the current treatment approach to the COVID-19 disease since they provide readily available options that can alleviate the severity of the disease and, hence, the prognosis of patients. That is why their effectiveness relies on the correct administration time and choosing the patient with suitable characteristics regarding the presence of comorbidities and the likelihood of the critical further development of the process.

Differences in incidence, nature of symptoms, and duration of long COVID among hospitalised migrant and non-migrant patients in the Netherland: a retrospective cohort study

Abstract Background and aim Comprehensive data on long-COVID across ethnic and migrant groups are lacking. We investigated incidence, nature of symptoms, clinical predictors, and duration of long-COVID among COVID-19 hospitalised patients in the Netherlands by migration background. Methods We used COVID-19 admissions and follow up data (January 2021-July 2022) from Amsterdam University Medical Centers. We calculated long-COVID incidence proportions by migration background and assessed for clinical predictors via robust Poisson regressions. We then examined associations between migration background and long COVID using robust Poisson regressions and adjusted for derived clinical predictors, and other biologically relevant factors. Results 1886 patients were included. 483 patients had long-COVID (26%, 95% CI 24-28%) at 12 weeks post-discharge. Symptoms like dizziness, joint pain, and headache varied by migration background. Clinical predictors of long-COVID were female sex, hospital admission duration, intensive care unit admission, and receiving oxygen, or corticosteroid therapy. Long-COVID risk was higher among patients with migration background than Dutch origin patients after adjustments for derived clinical predictors, age, smoking, vaccination status, comorbidities and remdesivir treatment. Conclusions There are significant differences in occurrence, nature of symptoms, and duration of long-COVID by migration background. Studies assessing functional limitations and access to post-COVID healthcare are needed to help plan for appropriate and accessible healthcare interventions.

Remdesivir triphosphate is a valid substrate to initiate synthesis of DNA primers by human PrimPol

Remdesivir is a broad-spectrum antiviral drug which has been approved to treat COVID-19. Remdesivir is in fact a prodrug, which is metabolized in vivo into the active form remdesivir triphosphate (RTP), an analogue of adenosine triphosphate (ATP) with a cyano group substitution in the carbon 1’ of the ribose (1’-CN). RTP is a substrate for RNA synthesis and can be easily incorporated by viral RNA-dependent RNA polymerases (RdRp). Importantly, once remdesivir is incorporated (now monophosphate), it will act as a delayed chain terminator, thus blocking viral RNA synthesis. It has been reported that mitochondrial Polγ is also blocked in vitro by RTP, but the low impact in vivo on mitochondrial DNA replication stalling is likely due to repriming by the human DNA-directed DNA Primase/Polymerase (HsPrimPol), which also operates in mitochondria. In this work, we have tested if RTP is a valid substrate for both DNA primase and DNA polymerase activities of HsPrimPol, and its impact in the production of mature DNA primers. RTP resulted to be an invalid substrate for elongation, but it can be used to initiate primers at the 5´site, competing with ATP. Nevertheless, RTP-initiated primers are abortive, ocassionally reaching a maximal length of 4–5 nucleotides, and do not support elongation mediated by primer/template distortions. However, considering that the concentration of ATP, the natural substrate, is much higher than the intracellular concentration of RTP, it is unlikely that HsPrimPol would use RTP for primer synthesis during a remdesivir treatment in real patients.

Changes in memory and cognition during the SARS-CoV-2 human challenge study

Patient-reported outcomes and cross-sectional evidence show an association between COVID-19 and persistent cognitive problems. The causal basis, longevity and domain specificity of this association is unclear due to population variability in baseline cognitive abilities, vulnerabilities, virus variants, vaccination status and treatment. Thirty-four young, healthy, seronegative volunteers were inoculated with Wildtype SARS-CoV-2 under prospectively controlled conditions. Volunteers completed daily physiological measurements and computerised cognitive tasks during quarantine and follow-up at 30, 90, 180, 270, and 360 days. Linear modelling examined differences between 'infected' and 'inoculated but uninfected' individuals. The main cognitive endpoint was the baseline corrected global cognitive composite score across the battery of tasks administered to the volunteers. Exploratory cognitive endpoints included baseline corrected scores from individual tasks. The study was registered on ClinicalTrials.gov with the identifier NCT04865237 and took place between March 2021 and July2022. Eighteen volunteers developed infection by qPCR criteria of sustained viral load, one without symptoms and the remainder with mild illness. Infected volunteers showed statistically lower baseline-corrected global composite cognitive scores than uninfected volunteers, both acutely and during follow up (mean difference over all time points=-0.8631, 95% CI=-1.3613,-0.3766) with significant main effect of group in repeated measures ANOVA (F (1,34)=7.58, p=0.009). Sensitivity analysis replicated this cross-group difference after controlling for community upper respiratory tract infection, task-learning, remdesivir treatment, baseline reference and model structure. Memory and executive function tasks showed the largest between-group differences. No volunteers reported persistent subjective cognitive symptoms. These results support larger cross sectional findings indicating that mild Wildtype SARS-CoV-2 infection can be followed by small changes in cognition and memory that persist for at least a year. The mechanistic basis and clinical implications of these small changes remain unclear. This study was funded through the UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy (BEIS) of Her Majesty's Government. WT was funded by the EPSRC through the CDT for Neurotechnology Imperial College London.

Antiviral drug treatment profiles and clinical outcomes of COVID-19 patients at public hospitals in Erbil city

Background & objectives: The World Health Organization has identified COVID-19 as a rapidly spreading global disease. Some antiviral drugs have shown promising efficacy in treating COVID-19. This study aims to identify the effects of antiviral drugs and compare them with other therapies in COVID-19 patients, while reviewing the clinical outcomes of these treatments. Methods: This observational retrospective case study included 451 COVID-19 patients, comprising 57.0% males and 43% females, conducted in Rizgari, Erbil, at Central Emergency, Rozhawa Emergency, and Emirate Hospitals over one year from December 2020 to December 2021. COVID-19 cases were confirmed using reverse transcriptase polymerase-chain reaction (RT-PCR) assays, and treatment followed the WHO guidelines, involving antivirals (Remdesivir, Favipiravir), broad-spectrum antibiotics (levofloxacin, azithromycin, ceftriaxone, meropenem, imipenem), and supportive treatment with Becozym (Vitamins B1 + B2 + B3 + B5 + B6). Data were recorded in the statistical department of the hospitals. Results: The total age range of the 451 patients was 95 (18-113) with a mean ± SD of 59.408 ± 18.26 years. The death rate was 22.39%. A majority of the survival patients were in the young age group (95.1%), while the death rate was higher in the old age group (more than 75 years). The death rate of patients treated with antiviral drug Remdesivir was 15.30%, while it was 37.93%, 73.45%, 15.25%, and 14.15% in patients on levofloxacin, ceftriaxone, meropenem, and Becozyme, espectively. Logistic regression analysis did not show any role of treatments in decreasing mortality. Conclusions: Significant differences were observed in clinical outcomes; the majority of surviving patients were in the young age group, while older COVID-19 patients had worse illnesses and treatment outcomes. Diabetes and hypertension were significant predictors of COVID-19 mortality. Although Remdesivir treatment showed a statistically significant association between survival and death cohorts, it was not considered a predictor variable for survival. Antibiotics and supplement drugs like Becozyme were also not considered predictors of survival for COVID-19 patients.

COVID-19 throughout pandemic waves and virus variants: a real-life experience in an Italian hospital.

New therapies and vaccines changed the management of COVID-19. The aim of this retrospective study was to describe characteristics, in-hospital mortality and its predictors in patients with moderate/severe COVID-19, considering the 4 different pandemic waves and viral variants' prevalence from February 2020 to January 2022. Among 1135 patients included, 873 (77%) had at least one comorbidity, 177 (16%) were immunocompromised. From waves 1 to 4, patients with severe respiratory failure and ICU admission decreased over time (p < 0.001), like the length of in-hospital stay (p < 0.001). Despite a reduction of in-hospital mortality from 19% to 11%, increased risk of death was related to older age and immunocompromising conditions, especially during the 4th wave (HR = 5.07 and HR = 10.86, p < 0.001 respectively) while remdesivir treatment in the 3rd wave (HR = 0.41, p = 0.010) and positive serology (aHR = 0.66, p = 0.027) were protective for survival. These data support the need for tailoring vaccine campaign for future COVID-19 waves.

Outpatient remdesivir treatment program for hospitalized patients with coronavirus disease-2019: Patient perceptions, process and economic impact

BackgroundRemdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In a prior work, patients who continued remdesivir in an outpatient setting experienced better 28-day clinical outcomes. Here, we assessed patients' perspectives and the economic impact of this outpatient practice. MethodsHospitalized patients who received remdesivir for COVID-19 at Mayo Clinic, Rochester, from 11/6/2020 to 11/5/2021 and were dismissed to continue remdesivir in the outpatient setting were surveyed. The cost of care was compared between those who remained hospitalized versus those who were dismissed. Results93 (19.8 %) among 470 eligible patients responded to the electronic survey. Responders were older than non-responders. The majority (70.5 %) had symptoms resolved by the time of the survey. Ten (11.4 %) patients had persistent symptoms attributed to long COVID-19. The majority were satisfied with the quality of care (82.3 %) and overall experience (76.0 %) in the infusion clinic. After adjusting for gender, comorbidity score, and WHO severity scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p < .01). An estimate of 1,077 hospital bed-days were made available to other patients as a result of this transition to outpatient. ConclusionAn outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital beds for other patients needing critical services.

The effect of early versus late remdesivir treatment in hospitalized mild to moderate COVID-19 patients in the Omicron era: A retrospective study.

Although real-world studies have found that remdesivir is effective in preventing poor prognosis, more information is needed on the optimal timing of remdesivir administration in high-risk coronavirus disease 2019 (COVID-19) patients in the Omicron era. From February 2022 to January 2023, a single-center retrospective study was performed in Korea. We compared the clinical characteristics and treatment outcomes between early (remdesivir treatment within 0-3 days from symptom onset) and late (≥ 4 days from symptom onset) treatment groups of patients who received remdesivir monotherapy. Of 284 patients, 225 were classified into the early treatment group and 59 were classified into the late treatment group. The early treatment group had a lower rate of 28-day progression to severe disease than the late treatment group (1.4% vs 7.4%, P = .03). Delaying remdesivir treatment ≥ 4 days from symptom onset (adjusted odds ratio [aOR], 6.17; 95% CI, 1.18-32.44; P = .03) and Charlson comorbidity index ≥ 3 (aOR, 9.62; 95% CI, 1.65-56.10; P = .01) were independent risk factors for 28-day progression to severe disease. Our results suggest that early administration of remdesivir could be associated with better prognosis in COVID-19 patients with the Omicron variant, and within 3 days from symptom onset seems to be the appropriate timing.

Early Outpatient Administration of Remdesivir Shortens Recovery Time in Patients with Mild to Moderate COVID-19

Background: During COVID-19, healthcare systems in underdeveloped nations had significant challenges and were unlikely to offer the necessary care. It appears that a new, reliable healthcare model that prevents hospitalization is necessary to reduce the pressure that COVID-19 is putting on healthcare systems and patients. More particularly, as Remdesivir's use as an outpatient treatment for mild to severe SARS-CoV-2 infection has rarely been examined; we aimed to investigate in-depth comprehension of the effects of Remdesivir in these cases. Methods: In our two-month cross-sectional study, non-hospitalized patients with mild to moderate COVID-19 who were referred to the hospital for up to 5 days of Remdesivir treatment received 200 mg of Remdesivir intravenously on day 1, followed by 100 mg of Remdesivir once daily for the subsequent 4 days. Patients were divided into groups based on the time of starting Remdesivir treatment after the appearance of symptoms: group 1 less than and equal to 7 days, and group 2 more than 7 days. Two groups were evaluated for a correlation between Remdesivir administration time and clinical symptoms on days 1 and 14 (follow-up visits). Results: The study enrolled 273 eligible patients with a mean age of 47.5 years, of whom 112 were males and 125 were females. Results showed that patients who received Remdesivir in the first 7 days had less dyspnea (P-value&lt;0.0001) and lung involvement (P-value&lt;0.0001) than those who received it after 7 days at the end of the study. Patients who came later to receive Remdesivir also showed higher fatigue, AST, and ALT levels on the first day. Conclusions: Among patients with moderate COVID-19, those who received a 5-day course of Remdesivir within 7 days of the onset of symptoms had a statistically significant difference in clinical status compared with those who received their treatments later. However, the size of this finding has uncertain clinical importance.

Remdesivir for Treatment of COVID-19 Requiring Oxygen Support: A Cross-Study Comparison from Two Large, Open-Label Studies.

Remdesivir, an RNA-polymerase prodrug inhibitor approved for treatment of COVID-19, shortens recovery time and improves clinical outcomes. This prespecified analysis compared remdesivir plus standard-of-care (SOC) with SOC alone in adults hospitalized with COVID-19 requiring oxygen support in the early stage of the pandemic. Data for 10-day remdesivir treatment plus SOC from the extension phase of an open-label study (NCT04292899) were compared with real-world, retrospective data on SOC alone (EUPAS34303). Both studies included patients aged ≥18 years hospitalized with SARS-CoV-2 up to 30 May 2020, with oxygen saturation ≤94%, on room air or supplemental oxygen (all forms), and with pulmonary infiltrates. Propensity score weighting was used to balance patient demographics and clinical characteristics across treatment groups. The primary endpoint was time to all-cause mortality or end of study (day 28). Time-to-discharge, with a 10-day landmark to account for duration of remdesivir treatment, was a secondary endpoint. 1974 patients treated with remdesivir plus SOC, and 1426 with SOC alone, were included after weighting. Remdesivir significantly reduced mortality versus SOC (hazard ratio [HR]: 0.46, 95% confidence interval: 0.39-0.54). This association was observed at each oxygen support level, with the lowest HR for patients on low-flow oxygen. Remdesivir significantly increased the likelihood of discharge at day 28 versus SOC in the 10-day landmark analysis (HR: 1.64; 95% confidence interval: 1.43-1.87). Remdesivir plus early-2020 SOC was associated with a 54% lower mortality risk and shorter hospital stays compared with SOC alone in patients hospitalized with COVID-19 requiring oxygen support. ClinicalTrials.gov NCT04292899 and EUPAS34303.

Utility of SARS-CoV-2 Subgenomic RNA in Kidney Transplant Recipients Receiving Remdesivir.

There is no reliable microbiological marker to guide responses to antiviral treatment in kidney transplant recipients (KTR) with COVID-19. We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) RT-PCR before and after receiving treatment with remdesivir compared with genomic RNA (gRNA) RT-PCR and its use as a surrogate marker of viral replication. We analyzed gRNA and sgRNA at baseline and after remdesivir treatment in KTR who received remdesivir for SARS-CoV-2 infection from November 2021 to February 2022. Thirty-four KTR received remdesivir for SARS-CoV-2 infection. The median time since transplantation was 80months (IQR 3-321) and 75% of patients had previously received 3 doses of a mRNA SARS-CoV-2 vaccine. Three patients (8%) were classified with mild, 25 (73%) with moderate, and 6 (17%) with severe SARS-CoV-2 infection. Thirty-two (94%) patients received 5 doses of remdesivir and two patients received 2 doses. The median time between symptom onset to remdesivir treatment was 5days (IQR 3-8.5). The median days of hospitalization were 6 (IQR 2-112). gRNA was positive in all patients at baseline and after remdesivir. Five (15%) patients had negative sgRNA at baseline and 20 (59%) after receiving remdesivir. Patients presenting with negative sgRNA at baseline were discharged from hospital in≤6days without complications. Moreover, those with negative sgRNA after remdesivir therapy did not require ICU admission and had favorable outcomes. Nevertheless, patients with positive sgRNA after antiviral treatment presented worse outcomes, with 47% requiring ICU admission and the three (9%) recorded deaths in the study were in this group. Based on these data, we hypothesize that sgRNA may have clinical utility to help monitor virologic response more accurately than gRNA in KTR who receive remdesivir. Moreover, patients with negative sgRNA at baseline may not require antiviral treatment and others presenting positive sgRNA at day 5 could benefit from prolonged or combined therapies.

#1902 Remdesivir ameliorates ferroptotic renal injury in hamster after SARS-CoV-2 infection

Abstract Background and Aims The purpose of this study was to see how remdesivir affected renal ferroptotic damage in hamsters following a human Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. We evaluated the inhibitory effects of remdesivir on the ferroptosis of SARS-CoV-2 infection in a hamster infection model and in in vivo assays. Method To investigate the effect of SARS-CoV-2 on renal ferroptosis, we administered 2.5 × 104 p.f.u. SARS-CoV-2 via intranasal to hamster. In the initial study, animals were treated with remdesivir subcutaneously (s.c.) for 7 days beginning at various times in relation to virus challenge. After 5 days, kidney tissues were harvested. The effect of REMDESIVIR on SARS-CoV-2 infection and ferroptosis were evaluated by immunohistochemistry. Next, ferroptosis-related markers, glutathione peroxidase 4 (Gpx4), 4-hydroxynonenal (4-HNE), Acyl-CoA synthetase long chain family member 4 (Acsl4), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (Ho-1) were evaluated by quantitative PCR. Results In hamsters, SARS-CoV-2 resulted in high viral protein expression in the renal tubules and decreased renal tubular luminal diameter in periodic acid-Schiff (PAS) stained kidney sections. Remdesivir treatment decreased SARS-CoV-2-induced viral spike protein, HO-1, ferritin heavy chain1 (FTH1), ferritin light chain (FTL), and 4-HNE expression in renal tubular epithelial cells of hamsters in a dose-dependent manner. GPX4 expression suppression after infection was ameliorated by remdesivir administration. Increased ferroptosis-related mRNA marker (Gpx4, 4-HNE, Acsl4, Nrf2, Ho-1) expression in hamster kidneys was suppressed by remdesivir treatment. Conclusion All of our data suggest that remdesivir treatment ameliorated SARS-CoV-2 infection-induced ferroptosis in the kidney in a hamster model.

Remdesivir versus Favipiravir in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia: A Propensity Score-Matched Retrospective Cohort Study.

Remdesivir treatment was associated with a reduced 28-day mortality and recovery time among patients hospitalized with severe COVID-19. Favipiravir is broadly used to treat COVID-19. However, various studies have had conflicting results on the efficacy of favipiravir for COVID-19. We hypothesized that remdesivir is more effective in clinical outcomes regarding the 29-day mortality rates, length of stay, and recovery rate than favipiravir in patients with moderate to severe COVID-19 pneumonia. We performed a retrospective cohort study that included adult hospitalized COVID-19 pneumonia patients with hypoxemia. Patients were classified into two groups according to the antiviral drugs. Age, oxygen saturation, fraction of inspired oxygen, and Charlson comorbidity index were used for propensity score matching. The primary objective was to determine whether the type of antiviral agent is associated with 29-day mortality. Other outcomes were the 15-day recovery rate and the length of intensive care unit or hospital stay. A total of 249 patients with moderate to severe COVID-19 pneumonia were included. With an adjustment for propensity score-matched, there were 204 patients for further analysis (102 patients in each antiviral drug group). Remdesivir patients had higher Radiographic Assessment of Lung Edema (RALE) scores on Chest X-ray (14.32±9.08 vs 11.34±8.46; standardized mean difference =33.9%). The Charlson Comorbidity Index Scores were comparable. The prevalences of diabetes, obesity, hypertension, and non-HIV immunocompromised state were higher in the remdesivir group. Regarding the primary outcomes, after adjusting by diabetes, obesity, and RALE score, there was no difference in the 29-day mortality rate between both groups [26 patients (25.5%) in the remdesivir group vs 28 patients (27.5%) in the favipiravir group]. The Kaplan-Meier curve analysis at 29 days indicated no significant difference in cumulative survival rate. The two groups' adjusted hazard ratio was 0.72; 95% CI, 0.41 to 1.25, p=0.24. A Kaplan-Meier analysis on the 15-day cumulative survival rate observed a trend towards a higher survival rate in the remdesivir group (adjusted hazard ratio 0.41; 95% CI, 0.20 to 0.84; p= 0.02) The proportion of patients who recovered on day 15, the length of intensive care unit(ICU) stays, and the hospital stay were not different between remdesivir and favipiravir groups (62 patients (60.8%) vs 56 patients (54.9%), p=0.39; 11.48 ± 11.88 days vs 10.87 ± 9.31 days, p=0.69; and 16.64±14.28 days vs 16.59 ±11.31 days, p=0.98, respectively). In patients with moderate to severe COVID-19 pneumonia, Remdesivir did not demonstrate superior benefits over Favipiravir regarding 29-day mortality, 15-day recovery rates, or hospital and ICU stay lengths. However, further investigation into the 15-day cumulative survival rate revealed a trend towards improved survival in the Remdesivir group.

Evaluation of the Efficacy of Remdesivir for the Treatment of Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, SARS-CoV-2, has accounted for more than 1 000 000 deaths in the United States alone. In May 2020, the Food and Drug Administration issued an Emergency Use Authorization to allow the investigational use of intravenous remdesivir for the treatment of suspected or confirmed COVID-19 in hospitalized children and adults. Several other agents, such as hydroxychloroquine, dexamethasone, and tocilizumab have been investigated as potential treatment options; however, dexamethasone is currently the only agent that has been proven to reduce mortality in patients who require supplemental oxygen. The purpose of this study was to determine if initiation of remdesivir treatment in patients who presented with early symptoms of COVID-19 (defined as symptom onset < 7 days) had a significant impact on in-patient all-cause mortality compared to initiation of remdesivir treatment in patients who presented with symptom onset of at least 7 days. This ethics-committee-approved, retrospective, multicenter, double-arm study was conducted across 10 facilities in the HCA Healthcare West Florida Division. Adult inpatients age 18 and older with confirmed COVID-19 and administered intravenous remdesivir from May 1, 2020, to July 31, 2020, were included. Exclusion criteria included patients less than 18 years of age, the concomitant use of hydroxychloroquine or tocilizumab for any indication, or an estimated glomerular filtration rate less than 30 milliliters per minute. The primary outcome of this study was in-patient all-cause mortality. Secondary outcomes included total length of stay, time to discharge, oxygen requirements, and number of ventilator days. A total of 217 patients from facilities in the HCA Healthcare West Florida Division were evaluated for inclusion. The primary outcome of all-cause mortality occurred in 34.9% of patients with symptom onset of fewer than 7 days versus 31.0% of patients with symptom onset of at least 7 days (P = .57). There were no statistical differences found among the secondary outcomes. Time since symptom onset did not result in a statistically significant difference in all-cause mortality in patients who received intravenous remdesivir for the treatment of COVID-19.

Dynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19.

Numerous SARS-CoV-2 variant strains with altered characteristics have emerged since the onset of the COVID-19 pandemic. Remdesivir (RDV), a ribonucleotide analogue inhibitor of viral RNA polymerase, has become a valuable therapeutic agent. However, immunosuppressed hosts may respond inadequately to RDV and develop chronic persistent infections. A patient with respiratory failure caused by interstitial pneumonia, who had undergone transplantation of the left lung, developed COVID-19 caused by Omicron BA.5 strain with persistent chronic viral shedding, showing viral fusogenicity. Genome-wide sequencing analyses revealed the occurrence of several viral mutations after RDV treatment, followed by dynamic changes in the viral populations. The C799F mutation in nsp12 was found to play a pivotal role in conferring RDV resistance, preventing RDV-triphosphate from entering the active site of RNA-dependent RNA polymerase. The occurrence of diverse mutations is a characteristic of SARS-CoV-2, which mutates frequently. Herein, we describe the clinical case of an immunosuppressed host in whom inadequate treatment resulted in highly diverse SARS-CoV-2 mutations that threatened the patient's health due to the development of drug-resistant variants.

Assessing the effect of remdesivir alone and in combination with corticosteroids on time to death in COVID-19: A propensity score-matched analysis

BackgroundThis study aimed to evaluate the impact of remdesivir, alone or in combination with corticosteroids, on the time to death in COVID-19 patients. MethodsThis retrospective cohort study was conducted between March 20, 2020, and March 18, 2021, on 5318 patients with confirmed COVID-19 at three tertiary educational hospitals in Tehran, Iran. The treated group consisted of COVID-19 patients who received remdesivir, either alone or in combination with corticosteroids, while the untreated group included infected patients who did not receive these treatments. The two groups were matched by propensity score matching method, which adjusted for 92 confounding factors such as demographic, sign and symptom, clinical, and treatment-related factors, to provide balanced covariates between the treated and untreated groups. ResultsOf the 4,322 patients, 791 received remdesivir alone and 694 received remdesivir combined with corticosteroids. Among the patients who received remdesivir, 456 were male, and the mean (±standard deviation) age was 59.52±16.49 with a median hospitalization stay of 8 (interquartile range: 5–13) days. After applying the nearest neighbor propensity score matching method, there were no significant differences found in the hazard of death between patients who received remdesivir alone and those who did not receive treatment (hazard ratio: 0.94; 95 % confidence interval: 0.76, 1.16). In addition, the combination of remdesivir and corticosteroids was not associated with a reduced hazard of death (hazard ratio: 1.00; 95 % confidence interval: 0.80, 1.26). The median hospitalization stay was significantly longer in the group treated with remdesivir (alone/combined with corticosteroids) compared to the untreated group, both before and after matching. ConclusionNo association was observed between remdesivir treatment (alone/combined with corticosteroids) and a reduced hazard of death among COVID-19 patients. However, longer hospitalization stays were observed in patients receiving remdesivir, either alone or in combination with corticosteroids, compared to the untreated group.

Differences in Glutamate Dehydrogenase (GLDH) and Other Liver Biochemistry Levels before and after Remdesivir Treatment in COVID-19

Background: Remdesivir (RDV) is a broad-spectrum antiviral approved by the Food and Drug Administration (FDA) for the treatment of Covid-19 patients, known to have the potential to cause toxic effects on the liver. Routine monitoring of liver biochemical parameters such as AST, ALT, bilirubin, ALP and GGT, can help detect liver injury. Drug-induced liver injury, according to Hy's law, is characterized by an increase in ALT &gt; 5x ULN, or ALP &gt; 2x ULN, or an increase in ALT &gt; 3x and total bilirubin &gt; 2x ULN, simultaneously. Glutamate dehydrogenase (GLDH) is a sensitive and specific hepatic marker, which can detect liver injury and loss of mitochondrial integrity earlier than other liver biochemical parameters. This study aimed to analyze GLDH levels and liver biochemical parameters before and after RDV therapy in patients with Covid-19. We also analyze several factors that affect liver function and suggest renal function. Methods: This study used an observational analytical with a prospective cohort design, in a population of Covid-19 patients receiving RDV therapy at the infectious emergency department and isolation ward Dr. Soetomo Surabaya for September-November. Consecutive sampling was taken. The subject had drawn blood twice; once before therapy and 5 days after receiving intravenous RDV. GLDH examination is using sandwich ELISA method, while ALT, AST, ALP, GGT, direct and total bilirubin were determined spectrophotometrically. Mann-whitney, the Wilcoxon rank test and Spearman correlation test were used to analyze the data. Results: The number of samples was 34 participants with an average age of 52.47+15.21 years. Concomitant medications were dominated by n-acetylcysteine (94.1%), antioxidants (91.2%) and immunomodulators (82.4%). None of the subjects suffered liver injury induced by RDV according to Hy’s Law. Median GLDH serum levels before RDV treatment 1,14 U/L and after 5 days RDV administration 0,85 U/L (p=0,945), AST (36,4 U/L; 34, 00U/L; p=0,140), ALT (30,43 U/L; 30,20 U/L; p=0,301), DBI (0,15mg/dL; 0,24mg/dL; p=0,090), TBI (0,49mg/dL; 0,50mg/dL; p=0,567), ALP (85,0U/L; 87, 5 U/L; p=0,313) dan GGT (64,5U/L; 71,0U/L; p=0,871). The use of concomitant medication was thought to have protective properties against hepatocytes. Conclusion: After 5 days of RDV treatment, there is no evidence of liver injury. There are no significant differences in GLDH levels and other liver biomarker parameters compared to baseline. There is no difference in delta GLDH levels between groups with and without renal impairment.

Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 Not Requiring Supplemental Oxygen.

Remdesivir has demonstrated benefit in some hospitalized patients with coronavirus disease 2019 (COVID-19) on supplemental oxygen and in nonhospitalized patients breathing room air. The durability of this benefit across time periods with different circulating severe acute respiratory syndrome coronavirus 2 variants of concern (VOC) is unknown. This comparative effectiveness study in patients hospitalized for COVID-19 and not receiving supplemental oxygen at admission compared those starting remdesivir treatment in the first 2 days of admission with those receiving no remdesivir during their hospitalization across different VOC periods. Using a large, multicenter US hospital database, in-hospital mortality rates were compared among patients hospitalized for COVID-19 but not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir at hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization, using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality rates or discharge to hospice. Among the 121 336 eligible patients, 58 188 remdesivir-treated patients were matched to 17 574 unique patients not receiving remdesivir. Overall, 5.4% of remdesivir-treated and 7.3% in the non-remdesivir group died within 14 days, and 8.0% and 9.8%, respectively, died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in the in-hospital mortality rate compared with non-remdesivir treatment (14-day and 28-day adjusted hazard ratios [95% confidence interval], 0.75 [0.68-0.83] and 0.83 [0.76-0.90], respectively). This significant mortality benefit endured across the different VOC periods. Remdesivir initiation in patients hospitalized for COVID-19 and not requiring supplemental oxygen at admission was associated with a significantly reduced in-hospital mortality rate. These findings highlight a potential survival benefit when clinicians initiated remdesivir on admission across the dominant variant eras of the evolving pandemic.

Clinical outcomes of remdesivir in patients with COVID-19 infection: An observational study from a tertiary care hospital in Pakistan

Background: The primary objective was to assess the change in oxygenation status of patients after remdesivir treatment. Material and Methods: This retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi from September to December 2020. All patients aged &gt;18 years admitted with a positive reverse transcriptase-polymerase chain reaction for COVID-19 were included. Infection severity was subcategorized into two groups (moderate-to-severe and critical). We compared oxygenation status and assisted ventilation before and after remdesivir treatment. An analysis of outcomes between the groups was conducted using chi squares and the student t-test at a significance level of &lt;0.05. Results: We had 213 COVID-19 patients, of whom 114 (53.5%) received remdesivir during their hospital stay. 69 (60.5%) patients were male and the mean age was 52±12 years. 56 patients (49.1%) had moderate-to-severe infections. 21 out of 56 patients (37.5%) with moderate-to-severe COVID-19 infection while 47 out of 58 patients (81%) with critical COVID-19 required oxygen following remdesivir treatment (p-value: &lt;0.001). Out of 58 critical COVID-19 patients, 46 patients (79.3%) were on non-invasive ventilation and 12 patients (20.7%) were on invasive ventilation prior to remdesivir therapy. 22 out of 46 patients (47.8%) recovered from non-invasive ventilation after remdesivir treatment (p-value: &lt;0.001). 15 patients had mortality (13.1%) while the mean length of hospital stay with moderate-to-severe COVID-19 infection was 6.8 days and with critical COVID-19 infection was 11.3 days. Conclusion: The study emphasizes that remdesivir was found to be clinically beneficial in patients with moderate-to-severe COVID-19 infection. Besides improving oxygenation status, it also reduced mortality and shortened hospital stays. Keywords: Antiviral drug, COVID-19, Hypoxia, Noninvasive ventilation, Severe acute respiratory distress syndrome