Effectiveness and Optimal Timing of Azvudine in COVID-19 Patients: A Multi-center Retrospective Study in Beijing, China
Xinjie Han, Xiaobo Han, Yongqian Wang, Ze Wang, Junchang Cui, Weiguo Zhao, Guoxin Mo, Yuhong Liu, Mengli Zheng, Fei Xie, Kaifei Wang, Jiguang Meng, Xin Yuan, Zhihai Han, Kun Xiao, Pan Pan, Junping Sun, Mingyue Zhang, Xinxin Zhang, Haibo Cheng, Wuxiang Xie, Lixin Xie
doi:10.21203/rs.3.rs-3145554/v1
Background: Clinical effectiveness of Azvudine against coronavirus infection and optimal time for initiation of Azvudine treatment to hospitalized COVID-19 patients are not fully understood. Methods: This is a multi-center retrospective cohort study, and ve clinical centers of the Chinese People's Liberation Army General Hospital participated. From omicron pandemics, 6218 hospitalized patients con rmed with COVID-19 from December 10, 2022, to February 20, 2023, were retrieved for this study. After exclusions and propensity score matching , 428 Azvudine recipients and 428 controls were included with a follow-up of 28 days. The primary outcome was all-cause mortality during 28 days of hospitalization, and the secondary outcome was the proportion of patients with clinical improvement up to day 28. Results: The Azvudine group had a lower crude all-cause death rate when compared to the control group (2.82 per 1000 person-days vs. 4.52 per 1000 person-days; HR: 0.63, 95%CI: 0.40-1.00; P=0.038). Notably, the incidence rate of clinical improvement outcome was signi cantly higher in patients who received Azvudine within 5 days from the onset of symptoms, compared to the control group (Median days: 9 vs. 10; P=0.007). Subgroup analyses showed that chronic lung disease and corticosteroid treatment acted as protective factors (P=0.010; P=0.050). Conclusions: Clinical effectiveness of Azvudine in improving all-cause mortality in COVID-19 patients was seen, and initiation of Azvudine treatment within 5 days of the onset of symptoms was found to be signi cant. Additionally, the ndings revealed the protective effect of Azvudine in COVID-19 patients with chronic lung disease.
Ethical Approval This research was approved by the Ethics Committee of People's Liberation Army General Hospital (NO. 309202302230712). Informed consent was not required due to the retrospective nature of the study design.
Competing interests All authors in this study declare no competing con icts.
Authors' contributions Han Xinjie, Han Xiaobo, WY, WZ, XW and XL reviewed the literature, designed statistical analysis, conducted analyses, wrote the manuscript; CJ, ZW, MG, LY, Zheng Mengli, XF, WK, MJ, YX, HZ, and CH collected and analyzed clinical data, also contributed to the interpretation of the analysis; XK, PP, SJ, Zhang Mingyue and ZX prepared some paragraphs of the manuscript. All authors contributed to the interpretation of the analysis, critically reviewed and revised the manuscript, and approved the nal manuscript as submitted. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. This retrospective study was supported by China National Nature Science Foundation (82172109). Figure 4 The subgroup analysis of the effectiveness of Azvudine treatment in reducing all-cause death (A) and improving clinical improvement (B) Supplementary Files This is a list of supplementary les associated with this preprint. Click to download.
References
Chan, Yam, Zhang, Globally e cient non-parametric inference of average treatment effects by empirical balancing calibration weighting, J R Stat Soc Series B Stat Methodol,
doi:10.1111/rssb.12129Deng, Li, Sun, Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study, J Med Virol,
doi:10.1002/jmv.28756Deng, Li, Sun, Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study, J Med Virol,
doi:10.1002/jmv.28756Dian, Meng, Sun, Azvudine versus Paxlovid for oral treatment of COVID-19 in Chinese patients with pre-existing comorbidities, J Infect,
doi:10.1016/j.jinf.2023.05.012Ganatra, Dani, Ahmad, Oral nirmatrelvir and ritonavir in non-hospitalized vaccinated patients with Covid-19, Clin Infect Dis
General O Ce, of the National Health Commission. Notice on the issuance of Diagnosis and Treatment Protocol for novel coronavirus infection (trial version 10)
Liu, Chen, Lin, Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients, J Infect,
doi:10.1016/j.jinf.2020.03.005Najjar-Debbiny, Gronich, Weber, Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients, Clin Infect Dis,
doi:10.1093/cid/ciac443Radcliffe, Palacios, Azar, Real-world experience with available, outpatient COVID-19 therapies in solid organ transplant recipients during the omicron surge, Am J Transplant,
doi:10.1111/ajt.17098Ren, Luo, Yu, Randomized, Open-Label, Controlled Clinical Trial of Azvudine Tablets in the Treatment of Mild and Common COVID-19, a Pilot Study, Adv Sci (Weinh),
doi:2001435.10.1002/advs.202001435Ren, Luo, Yu, Randomized, Open-Label, Controlled Clinical Trial of Azvudine Tablets in the Treatment of Mild and Common COVID-19, a Pilot Study, Adv Sci (Weinh),
doi:2001435.10.1002/advs.202001435Silva, Abreu Cabral, Souza, Serial viral load analysis by DDPCR to evaluate FNC e cacy and safety in the treatment of mild cases of COVID-19, Front Med,
doi:10.3389/fmed.2023.1143485Sun, Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study, EClinicalMedicine,
doi:10.1016/j.eclinm.2023.101981Therneau, Grambsch, Pankratz, Penalized survival models and frailty, J Comput Graphical Stat
Xu, Yang, Zheng, The Pyrimidine Analog FNC Potently Inhibits the Replication of Multiple Enteroviruses, J Virol,
doi:10.1128/JVI.00204-20Zheng, Peng, Xu, Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis, J Infect,
doi:10.1016/j.jinf.2020.04.021
