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In the year 2019, a highly virulent coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, precipitating the outbreak of the illness known as coronavirus disease 2019 (COVID-19). The commonly employed reverse transcription polymerase chain reaction (RT-qPCR) methodology serves to estimate the viral load in each patient's sample by employing a standard curve. However, it is imperative to recognize that this technique exhibits limitations with respect to clinical diagnosis and therapeutic applications, since an advancement of the conventional polymerase chain reaction methods, digital polymerase chain reaction (digital PCR or DDPCR), enables the direct quantification and clonal amplification of nucleic acid strands. The primary divergence between dPCR and traditional PCR resides in their approaches to measuring nucleic acid quantities. In this study, we investigated the viral loads of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) within 461 participants. By employing both RT-qPCR and DDPCR techniques, we established a comparison between the quantification methodologies of the two approaches. Our findings illustrate that the quantification through DDPCR affords a superior means of monitoring viral load within lower respiratory tract samples, thus enhancing the assessment of disease progression, particularly in scenarios characterized by low viral loads. [ABSTRACT FROM AUTHOR]

Background: Several therapeutic drugs have been authorized for the treatment of patients with Coronavirus disease 2019 (COVID-19). However, further research on the mechanisms of action, efficacy, and target populations of these novel therapeutic drugs are necessary. This study included mild, moderate, severe, and critical COVID-19 patients to evaluate azvudine's effectiveness across different severity levels. Methods: We conducted a retrospective cohort study of patients with COVID-19 admitted to our hospital from December 1, 2022, to March 31, 2023. Patients were divided into retrospective cohorts receiving azvudine antiviral therapy and standard treatment, and were followed-up for up to 28 days. Results: Prior to data processing, azvudine treatment was associated with reduced mortality rates at 7 days (1.09/1000 persons vs. 5.06/1000 persons, P < 0.001) and 14 days (3.35/1000 persons vs. 5.65/1000 persons, P = 0.001). After propensity score matching, a decrease in mortality rates at 7 days (0.8/1000 persons vs. 6.29/1000 persons, P < 0.001), 14 days (3.42/1000 persons vs. 7.26/1000 persons, P < 0.001), and 28 days (4.33/1000 persons vs. 7.29/1000 persons, P = 0.003) were observed following azvudine treatment. After inverse probability of treatment weighting adjustment, the results were consistent with propensity score matching. In the clinical subgroup analysis, azvudine treatment intervention significantly reduced the 7-day (2.49/1000 persons vs. 14.59/1000 persons, P = 0.001 and 11.36/1000 persons vs. 66.99/1000 persons, P < 0.001), 14-day (5.22/1000 persons vs. 17.36/1000 persons, P < 0.001 and 17.08/1000 persons vs. 51.72/1000 persons, P = 0.002), and 28-day (7.58/1000 persons vs. 16.02/1000 persons, P = 0.014 and 20.43/1000 persons vs. 46.51/1000 persons, P = 0.008) mortality rates in hospitalized patients with severe and critical COVID-19. Conclusions: The study suggests that in hospitalized patients with COVID-19, azvudine treatment significantly reduces patient mortality rates in hospitalized COVID-19 infections, wherein the effects are more pronounced in severe and critical patients. [ABSTRACT FROM AUTHOR]

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]

Abstract Background Several therapeutic drugs have been authorized for the treatment of patients with Coronavirus disease 2019 (COVID-19). However, further research on the mechanisms of action, efficacy, and target populations of these novel therapeutic drugs are necessary. This study included mild, moderate, severe, and critical COVID-19 patients to evaluate azvudine’s effectiveness across different severity levels. Methods We conducted a retrospective cohort study of patients with COVID-19 admitted to our hospital from December 1, 2022, to March 31, 2023. Patients were divided into retrospective cohorts receiving azvudine antiviral therapy and standard treatment, and were followed-up for up to 28 days. Results Prior to data processing, azvudine treatment was associated with reduced mortality rates at 7 days (1.09/1000 persons vs. 5.06/1000 persons, P

Siqin Zhang,1,&ast; Songsong Tan,1,&ast; Bin Yang,2 Yaoyao Wu,3 Guohang Yuan,3 Fengjiao Chen,4 Lin Liu3,5 1Department of Endocrinology and Metabolism, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 2Department of Central Laboratory, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 3Department of Respiratory and Critical Medicine, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 4Research Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 5NHC Key Laboratory of Pulmonary Immunological Diseases (Guizhou Provincial People’s Hospital), Guiyang, Guizhou, 550002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Liu, Department of Respiratory and Critical Medicine, Guizhou Provincial People’s Hospital, NHC Key Laboratory of Pulmonary Immunological Diseases (Guizhou Provincial People’s Hospital), No. 83, Zhongshan East Road, Guiyang, 550002, Guizhou, People’s Republic of China, Tel +86 28 18685109665, Fax +86 28 85423459, Email liulin0956@163.comObjective: Azvudine is used to treat patients with the coronavirus disease 2019 (COVID-19). This study evaluated the clinical efficacy of azvudine in hospitalized patients with different severities of COVID-19 because few studies have described this in patients with severe and non-severe COVID-19.Methods: This retrospective study included hospitalized patients with COVID-19 in Guizhou Provincial People’s Hospital between December 2022 and January 2023. Azvudine-treated patients and controls were matched for sex, age, and disease severity at admission. Laboratory results and outcomes, including all-cause mortality, invasive mechanical ventilation, intensive care unit admission, and hospital stay length, were evaluated. Stratified analysis was used to explore the difference in the efficacy of azvudine in severe and non-severe COVID-19 patients.Results: No significant differences in all-cause mortality were observed between the 303 azvudine recipients and 303 matched controls. However, azvudine-treated patients had shorter hospital stays (8.34± 4.79 vs 9.17± 6.25 days, P=0.046) and higher lymphocyte improvement rates (21.5% vs 13.9%, P=0.019), with a more pronounced effect in patients with non-severe COVID-19 (length of hospital stay, 8.07± 4.35 vs 10.00± 6.29 days, P=0.001; lymphocyte improvement rate, 23.8% vs 12.8%, P=0.015).Conclusion: Azvudine treatment shortens hospital stay length and increases the rate of lymphocyte count improvement in patients with non-severe COVID-19, suggesting that azvudine may be a treatment option for these patients.Keywords: azvudine, COVID-19, severity, effectiveness, clinical outcome, hospital stay length

Abstract The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40–1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79–1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58–1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir.

Ximiao Yu,1,&ast; Ruiqi Luo,2,&ast; Guijuan Xie,2 Jiali Ji,3,4 Jiehong Wang,1 Xiyue Li,3 Xiaojun Qian,2 Xun Wang1,2,5 1Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Jiangnan University Medical Center, Jiangnan University (Wuxi No.2 People’s Hospital), Wuxi, Jiangsu Province, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Changzhou, Changzhou, Jiangsu Province, People’s Republic of China; 5Department of Medicine, Nantong University, Nantong, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xun Wang, Department of Pulmonary and Critical Care Medicine, Jiangnan University Medical Center, Jiangnan University (Wuxi No.2 People’s Hospital), Wuxi, Jiangsu Province, 214126, People’s Republic of China, Email 081104125@fudan.edu.cnPurpose: This retrospective study aims to compare the effectiveness and safety of four oral antiviral drugs including Simnotrelvir/Ritonavir, Nirmatrelvir/Ritonavir, Azvudine and Molnupiravir in hospitalized patients with Coronavirus Disease 2019 (COVID-19) in a real-world setting, providing evidence to guide clinical practice against COVID-19.Patients and Methods: Patients with mild or moderate COVID-19 hospitalized at Wuxi City’s Second People’s Hospital during December 2022 to June 2023 were included in this study. Patients were grouped by the antiviral drug received. The primary endpoint was the length of hospital stay. Patients were further divided into subgroups for stratified analysis, considering age, timing of medication, and drug mechanisms, to explore whether these factors could influence the treatment efficacy.Results: Of the enrolled 195 patients receiving any treatment, 42 received Nirmatrelvir/Ritonavir, 33 received Molnupiravir, 81 received Simnotrelvir/Ritonavir, and 39 received Azvudine. Patients in Nirmatrelvir/Ritonavir and Simnotrelvir/Ritonavir groups had significantly shorter hospital stays compared to those in Azvudine group (P < 0.05). No significant difference was observed in hospital stays between those initiating antiviral therapy within or more than five days after symptom onset (P = 0.1109). Among patients with comorbidities, the Nirmatrelvir/Ritonavir and Simnotrelvir/Ritonavir group showed shorter hospital stays than the Azvudine group (P < 0.05). No serious treatment-related adverse events were observed across the groups.Conclusion: In this retrospective study, Nirmatrelvir/Ritonavir and Simnotrelvir/Ritonavir exerts stronger potency on reducing duration of hospital stays in hospitalized patient with COVID-19, suggestive of a better choice for antiviral therapy. Patients who fail to take antiviral drugs in time after symptom onset would still benefit from these antiviral regimens. Additional well-designed clinical trials with large sample size are still needed to further confirm the effectiveness of these antivirals.Keywords: antivirals, COVID-19, molnupiravir, simnotrelvir/ritonavir, azvudine, nirmatrelvir/ritonavir

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]

The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40–1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79–1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58–1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir. [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

Background: COVID-19 pneumonia has spread across China and globally since late 2019, becoming a pandemic. Its extremely contagious nature as well as high morbidity and mortality rates have attracted widespread attention globally. For the treatment of SARS-CoV-2 pneumonia, two commonly used antiviral drugs in the clinic are nirmatrelvir/ritonavir(Paxlovid) and Azvudine, while the therapeutic efficacy of the two drugs and their impact on patient prognosis remain inconclusive. Therefore, the aim of this study is to investigate the effects of two antiviral drugs, Azvudine and Paxlovid, on the disease development and prognosis of patients with COVID-19. Methods: This study collected and analyzed in Inner Mongolia hospital treated 267 cases of COVID - 19 patients. According to the use of antiviral medications, the participants in this experiment were split into the Azvudine and Paxlovid groups. The effectiveness of the medications was evaluated using the length of hospitalization, Nucleic acid into negative time for the first time, and laboratory indices such as total protein, lymphocytes, leukocytes, albumin, creatinine, and platelets. Results: Compared with the Azvudine group, patients in the Paxlovid group had a shorter recovery time, a higher degree of rise in lymphocytes, a faster recovery of the immune system, a lower rise in creatinine, and a lesser renal burden, but patients in the Paxlovid group had a greater decrease in total protein. Conclusion: In assessing patient conditions for treatment selection, Paxlovid may be preferable for individuals with renal insufficiency or those exhibiting compromised immune responses. Conversely, for patients experiencing malnutrition or cirrhotic hypoproteinemia, Azvudine could be considered to mitigate the reduction in protein levels.

Thymus is the important immune organ, responsible for T cell development and differentiation. The lower circulating T counts have been observed in patients who died from COVID-19 compared with survivors. Azvudine, also known as FNC, is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 patients. In this study, single-cell transcriptome, proteomics, and parallel reaction monitoring (PRM) were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey thymus. The results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as FNC. Key enzymes involved in the FNC phosphorylation process, such as Dck, Cmpk1, and Nme2, were highly expressed in CD4+ T cells, CD8+ T cells, and DP (CD4+ CD8+) cells. Additionally, FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases, phosphoribosyl transferases, and deaminases, respectively. The robust phosphorylation capacity of the thymus for cytidine analogue drug FNC, and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection effect. This suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties, as an important factor during antiviral drug design.

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]

Background: Azvudine (FNC) is a novel small molecule antiviral drug for treating COVID‐19 that is available only on the Chinese market. Despite being recommended for treating COVID‐19 by the Chinese guidelines, its efficacy and safety are still unclear. This study aimed to evaluate the protective effect of FNC on COVID‐19 outcomes and its safety. Methods: We followed the PRISMA 2020 guidelines and searched the PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI) databases to evaluate studies on the effectiveness of FNC in treating COVID‐19 in China, focusing on mortality and overall outcomes. Additionally, its impact on the length of hospital stay (LOHS), time to first nucleic acid negative conversion (T‐FNANC), and adverse events was evaluated. The inclusion criterion was that the studies were published from July 2021 to April 10, 2024. This study uses the ROBINS‐I tool to assess bias risk and employs the GRADE approach to evaluate the certainty of the evidence. Results: The meta‐analysis included 24 retrospective studies involving a total of 11 830 patients. Low‐certainty evidence revealed no significant difference in mortality (OR = 0.91, 95% CI: 0.76–1.08) or LOHS (WMD = −0.24, 95% CI: −0.83 to 0.35) between FNC and Paxlovid in COVID‐19 patients. Low‐certainty evidence shows that the T‐FNANC was longer (WMD = 1.95, 95% CI: 0.36–3.53). Compared with the Paxlovid group, low‐certainty evidence shows the FNC group exhibited a worse composite outcome (OR = 0.77, 95% CI: 0.63–0.95) and fewer adverse events (OR = 0.63, 95% CI: 0.46–0.85). Compared with supportive treatment, low certainty shows FNC significantly reduced the mortality rate in COVID‐19 patients (OR = 0.61, 95% CI: 0.51–0.74) and decreased the composite outcome (OR = 0.67, 95% CI: 0.50–0.91), and very low certainty evidence shows significantly decreased the T‐FNANC (WMD = −4.62, 95% CI: −8.08 to −1.15). However, in very low certainty, there was no significant difference in LOHS (WMD = −0.70, 95% CI: −3.32 to 1.91) or adverse events (OR = 1.97, 95% CI: 0.48–8.17). Conclusions: FNC appears to be a safe and potentially effective treatment for COVID‐19 in China, but further research with larger, high‐quality studies is necessary to confirm these findings. Due to the certainty of the evidence and the specific context of the studies conducted in China, caution should be exercised when considering whether the results are applicable worldwide. Trial Registration: PROSPERO number: CRD42024520565 [ABSTRACT FROM AUTHOR]

Thymus is the important immune organ, responsible for T cell development and differentiation. The lower circulating T counts have been observed in patients who died from COVID-19 compared with survivors. Azvudine, also known as FNC, is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 patients. In this study, single-cell transcriptome, proteomics, and parallel reaction monitoring (PRM) were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey thymus. The results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as FNC. Key enzymes involved in the FNC phosphorylation process, such as Dck, Cmpk1, and Nme2, were highly expressed in CD4+ T cells, CD8+ T cells, and DP (CD4+ CD8+) cells. Additionally, FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases, phosphoribosyl transferases, and deaminases, respectively. The robust phosphorylation capacity of the thymus for cytidine analogue drug FNC, and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection effect. This suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties, as an important factor during antiviral drug design. The activation effect of FNC on the nucleoside metabolism system potentially contribute to its enrichment in the thymus and immune protection effect. [Display omitted] [ABSTRACT FROM AUTHOR]

This systematic review and meta‐analysis aimed to compare the effectiveness and safety of azvudine versus nirmatrelvir/ritonavir (Paxlovid) in treating coronavirus disease 2019 (COVID‐19). The researchers conducted searches on PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar until January 2024. The Cochrane risk of bias tool was utilised to evaluate the quality of the included studies, and data analysis was performed using Comprehensive Meta‐Analysis software. Thirteen studies, including 4949 patients, were analysed. The meta‐analysis results showed no significant difference between the azvudine and Paxlovid groups in terms of mortality rate (odds rate [OR] = 0.84, 95% confidence interval [CI]: 0.59–1.21), negative polymerase chain reaction (PCR) conversion time (standard mean difference [SMD] = 1.52, 95% CI: −1.07–4.11), and hospital stay (SMD = −0.39, 95% CI: −1.12–0.33). However, a significant difference was observed between the two groups in terms of intensive care unit admission (OR = 0.42, 95% CI: 0.23–0.75) and the need for mechanical ventilation (OR = 0.61, 95% CI: 0.44–0.86) in favour of azvudine. The incidence of adverse events in the azvudine group was significantly lower (OR = 0.66, 95% CI: 0.43–0.99). The certainty of evidence was rated as low and moderate. Azvudine and Paxlovid demonstrated similar effectiveness in reducing mortality rates, negative PCR conversion time and hospital stay. However, azvudine showed better effectiveness in improving other outcomes. Regarding the level of certainty of evidence, further research is needed to validate or challenge these results. [ABSTRACT FROM AUTHOR]

Background: Since the end of 2022, Azvudine was widely used to treat hospitalized coronavirus disease 2019 (COVID-19) patients in China. However, data on the real-world effectiveness of Azvudine against severe outcomes and post-COVID-19-conditions (PCC) among patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants was limited. This study evaluates the effectiveness of Azvudine in hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominance period. Methods: From 1 November 2022 to 1 July 2023, an SARS-CoV-2 Omicron BA.5 dominant period, we conducted a single-center retrospective cohort study based on hospitalized patients with laboratory-confirmed SARS-CoV-2 infection from a tertiary hospital in Shihezi, China. Patients treated with Azvudine and usual care were propensity-score matched (PSM) at a 1:1 ratio to a control group in which patients received usual care only, with matching based on covariates such as sex, age, ethnicity, number of preexisting conditions, antibiotic use at admission, and baseline complete blood cell count. The primary outcomes were all-cause death and short-term (60 days) PCC post discharge. The secondary outcomes included the initiation of invasive mechanical ventilation and PCC at long-term post discharge (120 days). Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) of Azvudine treatment for both all-cause death and invasive mechanical ventilation, and logistic regression models were used to estimate the odds ratios (OR) for short-term and long-term PCC. Subgroup analyses were performed based on a part of the matched covariates. Results: A total of 2,639 hospitalized patients with SARS-CoV-2 infection were initially identified, and 2,069 ineligible subjects were excluded from analyses. After matching, 297 Azvudine recipients and 297 matched controls were eligible for analyses. The incidence rate of all-cause death was relatively lower in the Azvudine group than in control group (0.007 per person, 95% confidence interval [CI]: 0.001, 0.024 vs 0.128, 95% CI: 0.092, 0.171), and the use of Azvudine was associated with a significantly lower risk of death (HR: 0.049, 95% CI: 0.012, 0.205). Subgroup analyses suggested protection of Azvudine against the risks of all-cause death among men, age over 65, patients without the preexisting conditions, and patients with antibiotics dispensed at admission. Statistical differences were not observed between the Azvudine group and the control group for the risks of invasive mechanical ventilation or short and long-term PCC. Conclusions: Our findings indicated that Azvudine was associated with lower risk of all-cause death among hospitalized patients with Omicron BA.5 infection in a real-world setting. Further investigation is needed to explore the effectiveness of Azvudine against the PCC after discharge. SUMMARY IN BRIEF: This study aims to evaluate the real-world effectiveness of Azvudine among hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominant epidemic phase. Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) for all-cause death. We found that the use of Azvudine was associated with a significantly reduced risk of all-cause death among hospitalized patients with SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

COVID‐19 can lead to adverse outcomes in patients with pre‐existing diseases. Azvudine has been approved for treating COVID‐19 in China, but the real‐world data is limited. It is aimed to investigate the efficacy of Azvudine in patients with COVID‐19 and pre‐existing cardiovascular diseases. Patients with confirmed COVID‐19 and pre‐existing cardiovascular diseases are retrospectively enrolled. The primary outcome is all‐cause death during hospitalization. Overall, 351 patients are included, with a median age of 74 years, and 44% are female. 212 (60.6%) patients are severe cases. Azvudine is used in 106 (30.2%) patients and not in 245 (69.8%). 72 patients died during hospitalization. After multivariate adjustment, patients who received Azvudine a lower risk of all‐cause death (hazard ratio: 0.431; 95% confidence interval: 0.252–0.738; p = 0.002) than controls. Azvudine therapy is also associated with lower risks of shock and acute kidney injury. For sensitivity analysis in the propensity score‐matched cohort (n = 90 for each group), there is also a significant difference in all‐cause death between the two groups (hazard ratio: 0.189; 95% confidence interval: 0.071–0.498; p < 0.001). This study indicated that Azvudine therapy is associated with better outcomes in COVID‐19 patients with pre‐existing cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Nucleoside analogs are a common form of chemotherapy that disrupts DNA replication and repair, leading to cell cycle arrest and apoptosis. Reactive oxygen species (ROS) production is a significant mechanism through which these drugs exert their anticancer effects. This study investigated a new nucleoside analog called FNC or Azvudine, and its impact on ROS production and cell viability in Dalton's lymphoma (DL) cells. The study found that FNC treatment resulted in a time- and dose-dependent increase in ROS levels in DL cells. After 15 and 30 min of treatment with 2 and 1 mg/ml of FNC, mitochondrial ROS production was observed in DL cells. Furthermore, prolonged exposure to FNC caused structural alterations and DNA damage in DL cells. The results suggest that FNC's ability to impair DL cell viability may be due to its induction of ROS production and indicate a need for further investigation. [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

Cheng-Yi Hu,1 Wen-Shuai Cui,1 Yi Lei,1 Yu-Wen Tang,1 Yan-Yan Zhang,1 Qi-Min Su,1 Fang Peng,2 Yun-Fei Zeng,1 Jia-Lin Song,1 Cheng-Na Luo,1 Yan Zhou,1 Xin-Yan Li,1 Zhu-Xiang Zhao1 1Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Department of Critical Care Medicine, the Third Affiliated Hospital of Guang Zhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Zhu-Xiang Zhao, Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510515, People’s Republic of China, Email zhaozhuxiang@126.comPurpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19).Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization.Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among “severe patients”, the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P< 0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P> 0.05), length of stay (P> 0.05), or hospital costs (P> 0.05).Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.Keywords: azvudine, nirmatrelvir/ritonavir, COVID-19, SARS-CoV-2

In our retrospective cohort study, we aim to explore whether Azvudine modifies the risk of death in COVID-19 patients. It was conducted on the medical records of patients, consecutively admitted for COVID-19 pneumonia to two hospitals in Chongqing, China. Based on Azvudine treatment exposure, the patients were divided into Azvudine group and non-Azvudine group. We used 1:2 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between Azvudine and non-Azvudine groups. There were 1072 patients included in our original cohort. With 1:2 ratio PSM, the Azvudine group included 195 patients and non-Azvudine group included 390 patients. The results showed that Azvudine treatment was associated with improved in-hospital mortality in overall population (OR 0.375, 95% CI 0.225–0.623, P

Xiang Zhao,1 Yuan Cheng,1 Meng Zhang,1 Bianba Qianda,2 Baima Zhouma,3 Bianba Yangzhen,3 Yao Zheng,4 Shuo Zhang,5 Huiying Zhao6 1Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, People’s Hospital of Tibet Autonomous Region, Lhasa, People’s Republic of China; 3Department of Tuberculosis, Third People’s Hospital of Tibet Autonomous Region, Lhasa, People’s Republic of China; 4Departments of Internal Medicine, Affiliated Hospital of Xizang Minzu University, Lhasa, People’s Republic of China; 5Department of Emergency Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 6Department of Intensive Care Unit, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yuan Cheng, Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, People’s Republic of China, Tel +86-13811659696, Fax +86-01083575753, Email softsnake@bjmu.edu.cnBackground: Nirmatrelvir-ritonavir, also known as paxlovid, is a widely used antiviral drug against coronavirus disease 2019 (COVID-19). Azvudine, a drug previously used to treat human immunodeficiency virus-1, has also been used to treat COVID-19 in China. However, only a few clinical studies have evaluated the effects of azvudine. Additionally, studies comparing nirmatrelvir-ritonavir with azvudine have been limited in number.Methods: We carried out a retrospective case‒control analysis at the Third People’s Hospital of the Tibet Autonomous Region. Eighty-two eligible patients with COVID-19 who received azvudine treatment were included. A total of 145 control patients who received nirmatrelvir-ritonavir treatment were selected by propensity score matching for age, sex, the severity of disease, and initial cycle threshold values. A comparison of the nucleic acid test negative conversion time, the length of hospitalization, and mortality rate was conducted.Results: Overall, the mean nucleic acid test negative conversion time was comparable between the nirmatrelvir-ritonavir and azvudine groups (7.0 [11.0, 15.0] vs 9.0 [6.0, 12.0] days, P=0.064). However, for patients with mild COVID-19, the nucleic acid test negative conversion time was significantly shorter in the nirmatrelvir-ritonavir group than in the azvudine group (6.0 [5.0, 8.0] vs 8.0 [6.0, 11.0] days, P=0.029). The nirmatrelvir-ritonavir group and the azvudine group did not differ significantly in length of hospitalization (8.0 [5.5,10.5] vs 8.0 [5.0,10.0] days, P=0.378). Regarding the mortality rate, there were 4 (2.8%) deaths in the nirmatrelvir-ritonavir group and 3 (3.7%) in the azvudine group (P=0.706).Conclusion: Azvudine is generally as effective as nirmatrelvir-ritonavir, but for patients with mild COVID-19, nirmatrelvir-ritonavir could suppress the virus more rapidly. For those who cannot be treated with nirmatrelvir-ritonavir, azvudine might be an effective therapy for COVID-19.Keywords: nirmatrelvir-ritonavir, azvudine, COVID-19, clinical outcome, high altitude

Summary: Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan–Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423–1.262) in the azvudine group 0.802 (0.435–1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805–3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546–3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the “National Key R&D Program of China” (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

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]

COVID-19, caused by SARS-CoV-2, is spreading worldwide, regardless of different continents, increasing the death toll to almost five million, with more than 300 million reported cases. Researchers have been fighting the greatest threats to human civilization. This report provides a glimpse of ongoing small-molecule research on COVID-19 drugs to save millions of lives, which may provide researchers with a better understanding of rigorously investigated therapeutic agents. This report emphasizes the chemical structures and mechanisms of activity along with drug target information for several small molecules, including marketable drugs and agents under investigation. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Modified nucleosides, particularly those with 4'‐modifications, are significant nucleosides used in antiviral treatments. The drug discovery campaign of Azvudine starts from 2′‐deoxynucleoside, followed by extensive modifications, such as introducing the 4'‐position substitutions, a 2'‐β‐fluoro atom, and changing the nucleobases. Azvudine acts potently toward various HIV‐1 strains by inhibiting HIV‐1 reverse transcription and preventing Vif‐induced A3G degradation, representing the first‐in‐class dual‐acting antiviral agent. In July 2021, the NMPA conditionally approved Azvudine as an adjunct therapy for adult patients with high levels of HIV‐1 virus load when combined with NRTIs or NNRTIs. Azvudine is capable of inhibiting SARS‐CoV‐2, as well as its variants, including Alpha, Beta, Delta, and Omicron. Clinical trials have revealed its real‐world effectiveness among hospitalized severely or critically ill COVID‐19 patients or those with pre‐existing conditions. On July 25th, 2022, the NMPA granted conditional authorization approving Azvudine as China's first domestic oral anti‐COVID‐19 agent. Generally, Azvudine at therapeutic doses is safe and well‐tolerated in clinical settings. Azvudine got approval from the National Health Commission and National Administration of Traditional Chinese Medicine on August 9th to be used in the "Diagnosis and Treatment Program for Novel Coronavirus Pneumonia (Ninth Edition)" for treating common COVID‐19 adult patients. On August 12th, 2022, it was also approved by the National Healthcare Security Administration to be added to the list of medical reimbursements. Of note, the achievements related to Azvudine were indexed in the China Basic Research Development Report in Thirty‐Five of 2022. Azvudine was also approved on January 5th, 2023, to be used in the "Diagnosis and Treatment Program for Novel Coronavirus Pneumonia (Tenth Edition)" for treating COVID‐19 patients. In February 2023, the Ministry of Health of the Russian Federation approved the usage of Azvudine among individuals infected with SARS‐CoV‐2. What is the most favorite and original chemistry developed in your research group? My favorite chemistries are always those that enable efficient access to drug molecules. How do you get into this specific field? Could you please share some experiences with our readers? The virus uses nucleosides as raw materials for replication. Learned from this biological process, I have been devoted to, for decades, synthesizing nucleoside mimics. Once attached to the 3'‐hydroxy group of the virus RNA chain, these nucleoside analogs can effectively inhibit virus replication. Hard work pays off! We have developed a series of novel 4'‐modified nucleosides, among which Azvudine has been officially approved for treating HIV in China and COVID‐19 in both China and Russia. Notably, Azvudine is the first Chinese oral anti‐COVID‐19 agent. The experiences I would like to share with the readers are many, but emphases are placed on thinking critically and working enthusiastically. How do you supervise your students? I generally supervise students differently according to their aptitudes. For those keen on scientific work, I always suggest them learn from the literature, and practice makes perfect, think critically, and work with passion. What is the most important personality for scientific research? The personalities such as curiosity, creativity, persistence, and the ability to think critically and solve problems matter most for scientific research. Furthermore, what sets successful scientists apart is their passion for their work and their ability to persevere in facing challenges and setbacks. Who influences you mostly in your life? My Ph.D. supervisor profoundly fuels my passion for academia and, to some extent, reshapes my personality. [ABSTRACT FROM AUTHOR]

To examine the effectiveness of azvudine and nirmatrelvir–ritonavir in treating hospitalized patients with moderate‐to‐severe COVID‐19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate‐to‐severe COVID‐19 without contraindications for azvudine or nirmatrelvir–ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir–ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all‐cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent‐to‐treat analyses, azvudine reduced all‐cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12–0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24–0.92). Nirmatrelvir–ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17–1.05), and its composite with all‐cause death (HR: 0.38; 95% CI: 0.18–0.81). The study did not identify credible subgroup effects. The per–protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir–ritonavir improved the prognosis of hospitalized adults with moderate‐to‐severe COVID‐19 [ABSTRACT FROM AUTHOR]

Abstract Introduction Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China. Methods This retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion (P NANC), time to first nucleic-acid negative conversion (T FNANC), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes. Results This study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56–3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78–3.60; P = 0.189), P NANC (HR 0.87; 95% CI 0.69–1.09; P = 0.220), length of stay (β − 0.82; 95% CI − 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer T FNANC (β 2.53; 95% CI 0.76–4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses. Conclusion Azvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes. Graphical Abstract

Background Azovudine is a widely used antiviral drug for COVID-19 in China, but published trials on its effect on hepaticand renal function are extremely scarce. Objective To explore the changes of in hepatic and renal function in patients with COVID-19 infection after using Azovudine, so as to provide a reference for thesafe use of Azovudine in patients with renal insufficiency. Methods Inpatients ina tertiary general hospitalwho used Azovudine for COVID-19 from December 26, 2022 to December 31, 2022 were consecutively included in the retrospective study and divided into the normal group, mild injury group, moderate injury group, severe injury group, and end-stage groupaccording to estimated glomerularrate (eGFR) levels. The changes of biochemical parametersof liver and kidney including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), total bilirubin (TB), serum creatinine (Scr), eGFR were observed in each group; the formula D_FR=D_NL×[1-F_k (1-K_f) ] was used to correct the maintenance dose of Azivudine in patients with eGFR0.05) ; because the patients with moderate and severe renal injury were dose-corrected with Azivudine, the safety of this population was not compared if the dose was not corrected. Conclusion The use of Azivudine is prone to cause the elevation of ALT level and the decrease of eGFR, but the injury with clinical significance is 2.6% and 3.7%, respectively; there was no aggravation of liver and kidney injury in patients with moderate and severe kidney injury after using the corrected dose of Azivudine, however, this conclusion needs to be confirmed in a multicenter randomized controlled study with a large sample.

In our retrospective cohort study, we aim to explore whether Azvudine modifies the risk of death in COVID-19 patients. It was conducted on the medical records of patients, consecutively admitted for COVID-19 pneumonia to two hospitals in Chongqing, China. Based on Azvudine treatment exposure, the patients were divided into Azvudine group and non-Azvudine group. We used 1:2 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between Azvudine and non-Azvudine groups. There were 1072 patients included in our original cohort. With 1:2 ratio PSM, the Azvudine group included 195 patients and non-Azvudine group included 390 patients. The results showed that Azvudine treatment was associated with improved in-hospital mortality in overall population (OR 0.375, 95% CI 0.225–0.623, P < 0.001), severe subgroup (OR 0.239, 95% CI 0.107–0.535, P = 0.001), critical subgroup (OR 0.091, 95% CI 0.011–0.769, P = 0.028) in matched cohort with univariate analysis. And there was a significantly lower in-hospital mortality in overall population (11% vs. 24%, P ＜0.001), severe sub-group (10% vs. 32%, P < 0.001) and critical sub-group (5% vs. 34%, P = 0.017) in matched cohort. These results suggest Azvudine can reduce in-hospital mortality in overall COVID-19 patients, severe, and critical subgroup population. Whether Azvudine can reduce the in-hospital mortality of COVID-19 patients is an interesting question. In this manuscript, Azvudine's positive effect has been proved. [Display omitted] [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]

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The COVID-19 pandemic has caused significant losses and suffering around the world. Although the SARS-CoV-2 vaccine has largely controlled the spread of the virus, the scientific and sustainable treatment of COVID-19 patients is still necessary to truly end the pandemic. Small-molecule drugs against COVID-19 have attracted the attention of the scientific community and industry owing to their unique advantages such as a simple delivery method, relatively high output, and immune response with lower probability. Fortunately, in the last three years, some potentially effective drugs have been proposed, and have achieved good results in clinical trials. This paper briefly introduces the research progress on small-molecule drugs since 2020 to provide reference for future SARS-CoV-2 research. [ABSTRACT FROM AUTHOR]

There is no antiviral study on hemodialysis patients infected with coronavirus disease 2019 (COVID‐19), especially on the application of 2′‐deoxy‐2′‐β ‐fluoro‐4′‐azidocytidine (Azvudine, FNC) antiviral therapy. We conducted a multicenter observational study involving 1008 hemodialysis patients. After matching for age, sex, and other factors, 182 patients in the basic treatment group and 182 in the FNC group were included. The negative nucleic acid conversion rate of the FNC group was significantly higher than that of the basic treatment group, and viral loads, interleukin‐6, and C‐reactive protein were significantly lower than those of the basic treatment group (p < 0.05). There were no significant differences in liver function, renal function, or the number of adverse events between the two groups (p > 0.05). In conclusion, our study has provided novel evidence suggesting that the FNC scheme may be safe and effective compared to the basic treatment of hemodialysis patients with common COVID‐19. [ABSTRACT FROM AUTHOR]

Introduction: Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China. Methods: This retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion (PNANC), time to first nucleic-acid negative conversion (TFNANC), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes. Results: This study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56–3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78–3.60; P = 0.189), PNANC (HR 0.87; 95% CI 0.69–1.09; P = 0.220), length of stay (β − 0.82; 95% CI − 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer TFNANC (β 2.53; 95% CI 0.76–4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses. Conclusion: Azvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes. [ABSTRACT FROM AUTHOR]