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Background: Little is known about immunophenotyping characteristics and clinical outcomes of COVID-19 patients treated with azvudine during the Omicron variant surge. Methods: This study enrolled patients diagnosed with COVID-19 from December 2022 to February 2023. The primary outcome was defined as all-cause mortality, along with a composite outcome reflecting disease progression. The enrolled patients were followed for a period of 60 days from their admission. Results: A total of 268 COVID-19 patients treated with azvudine were enrolled in this retrospective study. The study found that the counts of lymphocyte subsets were significantly reduced in the composite outcome and all-cause mortality groups compared to the non-composite outcome and discharge groups (all p < 0.001). Correlation analysis revealed a negative association between lymphocyte subsets cell counts and inflammatory markers levels. The receiver operating characteristic (ROC) curve analysis identified low CD4+ T cell count as the most significant predictor of disease progression and all-cause mortality among the various lymphocyte subsets. Additionally, both the Kaplan-Meier curve and multivariate regression analysis demonstrated that low CD4+ T cell count level (< 156.00 cells/μl) was closely associated with all-cause mortality in COVID-19 patients treated with azvudine. Conclusions: A low CD4+ T cell count may serve as a significant predictive indicator for identifying COVID-19 patients receiving azvudine treatment who are at an elevated risk of experiencing adverse outcomes. These findings may offer valuable insights for physicians in optimizing the administration of azvudine. [ABSTRACT FROM AUTHOR]

Background: Azvudine (AZV), the first Chinese oral anti-coronavirus disease 2019 (COVID-19) drug, has shown substantial clinical benefits to viral clearance and prognosis in patients with mild and common COVID-19. However, there is no evidence in severe hospitalized COVID-19 patients. Methods: In this multicenter study, we analyzed 209 severe hospitalized COVID-19 patients in four hospitals. All the clinical data and the 28-day composite outcomes were recorded. All of the patients were categorized into two groups according to drug: the dexamethasone (DXM) group and the azvudine plus dexamethasone (AZV+DXM) group. Results: There were no differences in sex, age, BMI, and underlying diseases between the two groups. The ratio of the 28-day composite outcome was lower for the AZV+DXM group than that for the DXM group (16.97% vs. 31.82%, p = 0.029). The viral clearance time was shorter in the AZV+DXM group than in the DXM group (7.32 ± 2.57 vs. 8.55 ± 2.34 days, p = 0.017). The PaO2/FiO2 levels on day 5 (258.89 ± 55.22 vs. 233.12 ± 60.51, p = 0.026) and day 10 (289.48 ± 44.09 vs. 261.52 ± 37.34, p = 0.015) were higher in the AZV+DXM group than the DXM group. However, data on the hospitalization duration of the two groups were similar. Cox analysis showed the benefit of AZV+DXM in the subgroups of ≥65 years old, multiple organ dysfunction syndrome (MODS), cerebrovascular disease, C-reactive protein (CRP) ≥70mg/L, and D-dimer ≥1 µg/L. Conclusion: This study is the first to indicate that treatment with AZV+DXM might benefit severe Omicron-infected patients compared with DXM treatment alone. This finding demonstrates, at least partly, the necessity of antiviral treatment in severe patients. [ABSTRACT FROM AUTHOR]

Background: Azvudine, a repurposed oral small molecule antiviral drug, has potential effects in combating the SARS-CoV-2 virus. However, studies on its clinical efficacy in patients with COVID-19 are still limited and controversial, and further research and validation are necessary. Methods: A retrospective cohort study was conducted on COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command from 1 December 2022 to 31 January 2023. We included 132 patients treated with Azvudine and 132 controls after screening and propensity score matching. The primary outcomes including all-cause mortality and a composite outcome of disease progression such as non-invasive respiratory support, invasive respiratory support, admission to intensive care unit (ICU), and death were compared. Results: Azvudine recipients had a much lower incidence rate of composite disease progression outcome than controls (13.9075/1000 person-days versus 25.7731/1000 person-days, P <0.05). Azvudine recipients also possessed a lower all-cause mortality rate than controls (2.6797/1000 person-days versus 8.5910/1000 person-days, P <0.01). Azvudine treatment significantly reduced the risk of composite disease progression (HR: 0.37, 95% CI: 0.16-0.84, P =0.017) and all-cause death (HR: 0.25, 95% CI: 0.08-0.81, P =0.021) after adjusting potential confounding factors such as age, sex, severity of COVID-19, complications, concomitant therapy, time from symptoms to treatment, and important laboratory indicators. The subgroup analyses of composite disease progression outcome and all-cause death indicated robustness of Azvudine's in treating COVID-19 patients in general. Conclusion: Our study demonstrates that Azvudine has a significant positive impact on the clinical recovery of hospitalized patients with COVID-19. These findings provide important support for the use of Azvudine as a therapeutic option for COVID-19, given the current divergent views on its therapeutic efficacy and its importance in public health and medical care. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of this study was to explore the clinical characteristics of patients infected with different Omicron subvariants presenting non-severe disease, evaluate the safety and efficacy of Azvudine for treatment of COVID-19, in order to broaden understanding of Omicron subvariant infections.MethodA total of 244 individuals with Omicron subvariant (BA.2.76, n = 158; BA.5.1, n = 86) were included in the study. Demographic, clinical, and laboratory data of the study participants were collected and analyzed.ResultPatients infected with BA.5.1 exhibited a higher incidence of clinical symptoms like fatigue (25.58% vs. 2.53%, p

Introduction: Numerous studies have explored the treatment outcomes of Nirmatrelvir-Ritonavir and Azvudine in older patients with COVID-19. However, direct comparisons between these two drugs are still relatively limited. This study aims to compare the safety and effectiveness of these two drugs in Chinese older patients with early infection to provide strategies for clinical treatment. Methods: Older COVID-19 patients (age =65) hospitalized during the winter 2022 epidemic in China were included and divided into Nirmatrelvir-Ritonavir and Azvudine. Demographics, medication information, laboratory parameters, and treatment outcomes were collected. All-cause 28-day mortality, delta cycle threshold (ΔCt), nucleic acid negative conversion time, and incidence of adverse events were defined as outcomes. Propensity score matching (PSM), Kaplan-Meier, Cox proportional hazards model, subgroup analysis, and nomograms were selected to evaluate the outcomes. Results: A total of 1,508 older COVID-19 patients were screened. Based on the inclusion and exclusion criteria, 1,075 patients were eligible for the study. After PSM, the final number of older COVID-19 patients included in the study was 375, and there were no significant differences in demographic characteristics between the two groups (p > 0.05). Compared to the Azvudine group, the Nirmatrelvir-Ritonavir group showed a higher incidence of multiple adverse events (12.8% vs 5.2%, p = 0.009). The incidence of adverse events related to abnormal renal function was higher in the Nirmatrelvir-Ritonavir group compared to the Azvudine group (13.6% vs 7.2%, p = 0.045). There were no significant differences between the two groups in terms of all-cause 28-day mortality (HR = 1.020, 95% CI: 0.542 - 1.921, p = 0.951), whereas there were significant differences in nucleic acid negative conversion time (HR = 1.659, 95% CI: 1.166 - 2.360, p = 0.005) and ΔCt values (HR = 1.442, 95% CI: 1.084 - 1.918, p = 0.012). Conclusion: Azvudine and Nirmatrelvir-Ritonavir have comparable effectiveness in reducing mortality risk. Azvudine may perform better in nucleic acid negative conversion time and virus clearance and shows slightly better safety in older patients. Further studies with a larger sample size were needed to validate the result. [ABSTRACT FROM AUTHOR]

BackgroundLittle is known about immunophenotyping characteristics and clinical outcomes of COVID-19 patients treated with azvudine during the Omicron variant surge.MethodsThis study enrolled patients diagnosed with COVID-19 from December 2022 to February 2023. The primary outcome was defined as all-cause mortality, along with a composite outcome reflecting disease progression. The enrolled patients were followed for a period of 60 days from their admission.ResultsA total of 268 COVID-19 patients treated with azvudine were enrolled in this retrospective study. The study found that the counts of lymphocyte subsets were significantly reduced in the composite outcome and all-cause mortality groups compared to the non-composite outcome and discharge groups (all p < 0.001). Correlation analysis revealed a negative association between lymphocyte subsets cell counts and inflammatory markers levels. The receiver operating characteristic (ROC) curve analysis identified low CD4+ T cell count as the most significant predictor of disease progression and all-cause mortality among the various lymphocyte subsets. Additionally, both the Kaplan-Meier curve and multivariate regression analysis demonstrated that low CD4+ T cell count level (< 156.00 cells/μl) was closely associated with all-cause mortality in COVID-19 patients treated with azvudine.ConclusionsA low CD4+ T cell count may serve as a significant predictive indicator for identifying COVID-19 patients receiving azvudine treatment who are at an elevated risk of experiencing adverse outcomes. These findings may offer valuable insights for physicians in optimizing the administration of azvudine.

BackgroundAzvudine (AZV), the first Chinese oral anti-coronavirus disease 2019 (COVID-19) drug, has shown substantial clinical benefits to viral clearance and prognosis in patients with mild and common COVID-19. However, there is no evidence in severe hospitalized COVID-19 patients.MethodsIn this multicenter study, we analyzed 209 severe hospitalized COVID-19 patients in four hospitals. All the clinical data and the 28-day composite outcomes were recorded. All of the patients were categorized into two groups according to drug: the dexamethasone (DXM) group and the azvudine plus dexamethasone (AZV+DXM) group.ResultsThere were no differences in sex, age, BMI, and underlying diseases between the two groups. The ratio of the 28-day composite outcome was lower for the AZV+DXM group than that for the DXM group (16.97% vs. 31.82%, p = 0.029). The viral clearance time was shorter in the AZV+DXM group than in the DXM group (7.32 ± 2.57 vs. 8.55 ± 2.34 days, p = 0.017). The PaO2/FiO2 levels on day 5 (258.89 ± 55.22 vs. 233.12 ± 60.51, p = 0.026) and day 10 (289.48 ± 44.09 vs. 261.52 ± 37.34, p = 0.015) were higher in the AZV+DXM group than the DXM group. However, data on the hospitalization duration of the two groups were similar. Cox analysis showed the benefit of AZV+DXM in the subgroups of ≥65 years old, multiple organ dysfunction syndrome (MODS), cerebrovascular disease, C-reactive protein (CRP) ≥70mg/L, and D-dimer ≥1 µg/L.ConclusionThis study is the first to indicate that treatment with AZV+DXM might benefit severe Omicron-infected patients compared with DXM treatment alone. This finding demonstrates, at least partly, the necessity of antiviral treatment in severe patients.

BackgroundAzvudine, a repurposed oral small molecule antiviral drug, has potential effects in combating the SARS-CoV-2 virus. However, studies on its clinical efficacy in patients with COVID-19 are still limited and controversial, and further research and validation are necessary.MethodsA retrospective cohort study was conducted on COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command from 1 December 2022 to 31 January 2023. We included 132 patients treated with Azvudine and 132 controls after screening and propensity score matching. The primary outcomes including all-cause mortality and a composite outcome of disease progression such as non-invasive respiratory support, invasive respiratory support, admission to intensive care unit (ICU), and death were compared.ResultsAzvudine recipients had a much lower incidence rate of composite disease progression outcome than controls (13.9075/1000 person-days versus 25.7731/1000 person-days, P

Background: Current guidelines prioritize the use of Azvudine in Coronavirus Disease 2019 (COVID-19) patients, while biomarkers for prognosis in Azvudinetreated COVID-19 patients are still lacking. Here, we aim to assess the prognostic value of eosinopenia in Azvudine-treated COVID-19 patients. Methods: We retrospectively reviewed 290 consecutive Azvudine-treated hospitalized COVID-19 patients. Clinical characteristics and prognosis data were analyzed between patients with eosinopenia and with normal eosinophil levels. Results: A total of 290 patientswere enrolled in this study, with a median age of 69 years. Among them, 40.69% presented with eosinopenia and 59.31% had normal eosinophil levels. Common symptoms included cough (87.6%), expectoration (76.2%), fever (67.9%), poor appetite (47.2%), and polypnea (46.6%). Compared to patients with normal eosinophil levels, those with eosinopenia were older and less likely to experience fatigue (25.4% vs. 39.0%, P=0.016). Significant differences in laboratory parameters, particularly in blood routine and blood biochemical indicators, were observed between the two groups. Patients with eosinopenia were also less likely to develop severe illness subtypes, requiring more medication and oxygen support. The Cox proportional hazardmodel showed that eosinopenia was associated with worsening progression in Azvudine-treated COVID-19 patients (adjusted hazard ratio=2.79, 95% confidence interval: 1.04, 7.50), adjusting for potential confounders. Conclusion: Eosinopenia is associated with worsening prognosis in Azvudinetreated COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Azvudine has been approved in China for the treatment of COVID-19 patients. Previous studies have suggested a correlation between high levels of lactate dehydrogenase (LDH) and the severity of COVID-19. However, the impact of LDH levels in COVID-19 patients receiving Azvudine treatment remains unclear. Methods: In this retrospective cohort study, we analyzed the data of 351 hospitalized COVID-19 patients who were consecutively treated with Azvudine, with or without high LDH levels. The clinical features, treatment strategies and prognosis data were collected and analyzed. Results: Among the 351 hospitalized patients with COVID-19 treated with Azvudine (119 with high-LDH levels), the median age was 69 years (range 58-78), and 213 (60.7%) were male. Common symptoms included cough (86.0%), expectoration (73.5%), fever (69.8%), polypnea (47.6%) and poor appetite (46.4%). Patients with high LDH levels exhibited significantly elevated leucocyte and neutrophil counts, elevated level of myocardial enzymes, as well as higher levels of inflammatory markers such as interleukin-6, interleukin-10, procalcitonin, C reactive protein, ferritin, and prolonged erythrocyte sedimentation rate upon admission. COVID-19 patients with high-LDH levels had higher rates of corticosteroid therapy, non-invasive and invasive mechanical ventilation, worsened and death (2.5% vs. 0%). The Cox proportional hazard model demonstrated that high LDH levels (adjusted hazard ratio = 5.27; 95% confidence interval: 1.19, 14.50) were associated with a more unfavorable composite disease progression outcome among COVID-19 patients treated with Azvudine, after accounting for potential confounding variables. Conclusion: High-LDH levels predict a worse composite disease progression outcome in COVID-19 patients treated with Azvudine. [ABSTRACT FROM AUTHOR]

Background: Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety. Methods: We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded. Results: Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (p = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (p = 0.038) and the need for invasive mechanical ventilation (p = 0.035), while the in-hospital death event did not significantly differ (p = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (p = 0.565). Conclusion: In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. However, further confirmation through additional clinical trials is necessary. [ABSTRACT FROM AUTHOR]

Background: Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety.Methods: We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded.Results: Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (p = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (p = 0.038) and the need for invasive mechanical ventilation (p = 0.035), while the in-hospital death event did not significantly differ (p = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (p = 0.565).Conclusion: In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. However, further confirmation through additional clinical trials is necessary.

BackgroundIn 2019, a highly pathogenic coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced and resulted in the outbreak of coronavirus disease 2019 (COVID-19). With the aim of finding effective drugs to fight against the disease, several trials have been conducted since COVID-19 can only be considered a treatable disease, from a clinical point of view, after the availability of specific and effective antivirals. AZVUDINE (FNC), initially developed for treating HIV, is a potential treatment for COVID-19 as it has the capability to lower the patient’s viral load and promote recovery.MethodsVolunteers infected with SARS-CoV-2 confirmed by reverse transcription polymerase chain reaction (RT-PCR), with good kidney and liver function, who were not using other antivirals or monoclonal antibodies were eligible. Samples from patients were assessed for viral load every 48 h during treatment using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and droplet digital polymerase chain reaction (ddPCR).ResultsThe study’s primary outcome measure was the percentage of participants showing an improvement in clinical scores, while the secondary outcome measure was the percentage of participants with a clinical outcome of cure. These measures were used to assess the safety and efficacy of FNC for treating COVID-19. In the analysis of sociodemographic variables, no significant differences were detected between patients in the FNC and the placebo group for race, age group, or sex. The results showed a potential benefit to participants who received FNC during the study, as observed in the shorter hospital stay, shorter negative conversion time of SARS-CoV-2, and a significant reduction in viral load. Furthermore, the reduction in fever and chills were significant at D1, D2, and D3. In this study, a total of 112 adverse events cases were noted, with 105 cases being categorized as non-serious and only 7 cases as serious adverse events.ConclusionThe pandemic is not being effectively controlled and is causing multiple waves of infection that require extensive medical resources. However, FNC has demonstrated potential to reduce the treatment duration of moderate COVID-19 cases, thereby saving significant medical resources. This makes FNC a promising candidate for COVID-19 treatment.Clinical trial registration: [clinicaltrials.gov], identifier [NCT04668235].

Background: Azvudine (FNC) is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). However, drug interactions with azvudine have been poorly studied, especially with no reported cases of azvudine with anticoagulants such as warfarin and rivaroxaban. Case summary: The patient was diagnosed with lower limb venous thrombosis and took warfarin regularly. The international normalized ratio (INR) was stable (2.0-3.0). However, the INR increased to 7.52 after administering azvudine. The patient had no other factors justifying this change. This increase in INR occurred again with the administration of azvudine in combination with rivaroxaban, and the INR increased to 18.91. After azvudine administration was stopped, the INR did not increase when rivaroxaban was used alone. Conclusion: Azvudine, warfarin, and rivaroxaban might have previously unidentified drug interactions that increased the INR. Therefore, the INR must be closely monitored when they are concomitantly administered in COVID-19 patients. [ABSTRACT FROM AUTHOR]

IntroductionThe SARS-CoV-2 outbreak has threatened the human population globally as the numbers of reinfection cases even after large-scale vaccination. Trials have been carried out to find drugs effective in fighting the disease, as COVID-19 is being considered a treatable disease only after we have antivirals. A clinical candidate originally developed for HIV treatment, AZVUDINE (FNC), is a promising drug in the treatment of COVID-19.MethodsTo predict the clinical outcome of COVID-19, we examined the course of viral load, every 48 h, by RT-PCR, and disease severity using an antiviral drug, FNC, with 281 participants. A randomized clinical trial was performed to evaluate the efficacy of FNC added to standard treatment, compared with placebo group added to standard treatment, for patients with mild COVID-19. RT-qPCR and ddPCR were applied to estimate the viral load in samples from patients. Also, the clinical improvement was evaluated as well as the liver and kidney function.Results and discussionNotably, the FNC treatment in the mild COVID-19 patients may shorten the time of the nucleic acid negative conversion (NANC) versus placebo group. In addition, the FNC was effective in reducing the viral load of these participants. The present clinical trial results showed that the FNC accelerate the elimination of the virus in and could reduce treatment time of mild patients and save a lot of medical resources, making it a strong candidate for the outpatient and home treatment of COVID-19.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05033145, identifier NCT05033145.

Azvudine (FNC) is a novel cytidine analogue that has both antiviral and anticancer activities. This minireview focuses on its underlying molecular mechanisms of suppressing viral life cycle and cancer cell growth and discusses applications of this nucleoside drug for advanced therapy of tumors and malignant blood diseases. FNC inhibits positive-stand RNA viruses, like HCV, EV, SARS-COV-2, HBV, and retroviruses, including HIV, by suppressing their RNA-dependent polymerase enzymes. It may also inhibit such enzyme (reverse transcriptase) in the human retrotransposons, including human endogenous retroviruses (HERVs). As the activation of retrotransposons can be the major factor of ongoing cancer genome instability and consequently higher aggressiveness of tumors, FNC has a potential to increase the efficacy of multiple anticancer therapies. Furthermore, FNC also showed other aspects of anticancer activity by inhibiting adhesion, migration, invasion, and proliferation of malignant cells. It was also reported to be involved in cell cycle arrest and apoptosis, thereby inhibiting the progression of cancer through different pathways. To the date, the grounds of FNC effects on cancer cells are not fully understood and hence additional studies are needed for better understanding molecular mechanisms of its anticancer activities to support its medical use in oncology.

Azvudine (FNC) is a novel cytidine analogue that has both antiviral and anticancer activities. This minireview focuses on its underlying molecular mechanisms of suppressing viral life cycle and cancer cell growth and discusses applications of this nucleoside drug for advanced therapy of tumors and malignant blood diseases. FNC inhibits positive-stand RNA viruses, like HCV, EV, SARS-COV-2, HBV, and retroviruses, including HIV, by suppressing their RNA-dependent polymerase enzymes. It may also inhibit such enzyme (reverse transcriptase) in the human retrotransposons, including human endogenous retroviruses (HERVs). As the activation of retrotransposons can be the major factor of ongoing cancer genome instability and consequently higher aggressiveness of tumors, FNC has a potential to increase the efficacy of multiple anticancer therapies. Furthermore, FNC also showed other aspects of anticancer activity by inhibiting adhesion, migration, invasion, and proliferation of malignant cells. It was also reported to be involved in cell cycle arrest and apoptosis, thereby inhibiting the progression of cancer through different pathways. To the date, the grounds of FNC effects on cancer cells are not fully understood and hence additional studies are needed for better understanding molecular mechanisms of its anticancer activities to support its medical use in oncology. [ABSTRACT FROM AUTHOR]