The effectiveness and safety of azvudine treatment in COVID‐19 patients with kidney disease based on a multicenter retrospective cohort study
Bo Yu, Mengzhao Yang, Jia Yu, Daming Wang, Hong Luo, Ming Cheng, Shixi Zhang, Guotao Li, Ling Wang, Guowu Qian, Donghua Zhang, Silin Li, Zhigang Ren, Quancheng Kan
VIEW, doi:10.1002/viw.20240075
Kidney disease has been the main risk factor of poor prognosis for COVID-19 patients. The effectiveness and safety of azvudine treatment in COVID-19 patients with kidney disease have not been reported. Herein, we conducted a nine-center and retrospective cohort study in China (ClinicalTrials: NCT06349655) that enrolled 32,864 hospitalized COVID-19 patients, in which 4192 patients were pre-existed with kidney disease. After exclusions and propensity score matching, a total of 831 kidney disease patients treated with azvudine and 831 kidney disease patients treated without any anti-viral treatment (normal group) were selected. Based on Kaplan-Meier and Cox regression analysis, we found that azvudine administration had significantly decreased risks of all-cause death (p < 0.0001) and composite disease progression (p = 0.012) as compared Bo Yu, Mengzhao Yang, and Jia Yu contributed equally to this work.
S U P P O R T I N G I N F O R M AT I O N Additional supporting information can be found online in the Supporting Information section at the end of this article.
References
Bellocco, Pagano, None, Nutrition
Cai, Zhang, Zhu, Liu, Liu et al., None, Int. Urol. Nephrol
Cheng, Luo, Wang, Zhang, Wang et al., None, Kidney Int
China, COVID-19 diagnosis and treatment plan (trial version 10)
China, COVID-19 diagnosis and treatment plan (trial version 9)
Deng, Li, Sun, Jin, Zhou et al., None, J. Med. Virol
Domenech, Pérez, Saldarini, Uad, Musso, None, Int. Urol. Nephrol
Farhangfar, Kurgan, Dy, None, Pattern Recognit
Gibson, None, Am J. Kidney Dis
Gram, Emborg, Schelde, Friis, Nielsen et al., None, PLoS Med
Hughes, Heron, Sterne, Tilling, None, Int. J. Epidemiol
Kale, Shelke, Dagar, Anders, Gaikwad, None, Front. Pharmacol
Portolés, Marques, López-Sánchez, Valdenebro, Munez et al., None, Nephrol. Dial. Transplant
Ren, Luo, Yu, Song, Liang et al., None, Adv. Sci
Sai, Vijeth, Hemalatha, None, J. Assoc. Chest
Services, Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Shang, Fu, Geng, Zhang, Zhang et al., None, J. Med. Virol
Silver, Beaubien-Souligny, Shah, Harel, Blum et al., None, Kid. Med
Su, Yang, Wan, Yi, Tang et al., None, Kidney Int
Wei, Zeng, Wang, Gui, Zhang et al., None, Front. Pharmacol
Wen, Chen, Tang, Wang, Zhou et al., None, Ann. Med
Wu, Ma, Miao, Ye, Li et al., None, Front. Public Health
Yu, Chang, None, Signal Transduct. Target. Ther
Zhang, Wang, Deng, Liang, Su et al., None, J. Med. Virol
Zhu, None, Frontiers in Pharmacology
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"abstract": "<jats:title>Abstract</jats:title><jats:p>Kidney disease has been the main risk factor of poor prognosis for COVID‐19 patients. The effectiveness and safety of azvudine treatment in COVID‐19 patients with kidney disease have not been reported. Herein, we conducted a nine‐center and retrospective cohort study in China (ClinicalTrials: NCT06349655) that enrolled 32,864 hospitalized COVID‐19 patients, in which 4192 patients were pre‐existed with kidney disease. After exclusions and propensity score matching, a total of 831 kidney disease patients treated with azvudine and 831 kidney disease patients treated without any anti‐viral treatment (normal group) were selected. Based on Kaplan–Meier and Cox regression analysis, we found that azvudine administration had significantly decreased risks of all‐cause death (<jats:italic>p</jats:italic> < 0.0001) and composite disease progression (<jats:italic>p</jats:italic> = 0.012) as compared to the normal group. Multivariate Cox proportional hazards regression analysis demonstrated that the hazard ratio of all‐cause death was 0.64 (95% CI: 0.503–0.826, <jats:italic>p</jats:italic> < 0.001) and the hazard ratio of composite disease progression was 0.81 (95% CI: 0.658–1.004, <jats:italic>p</jats:italic> = 0.05). The subgroup analysis of different characteristics indicated no significant influence of single factor in both all‐cause mortality and composite disease progression. Five sensitivity analyses were employed to verify the robustness of our results. Safety analysis based on adverse event rate demonstrated an increased rate of hypertriglyceridemia after azvudine administration. In conclusion, we are the first to report the effectiveness and safety of azvudine treatment in COVID‐19 patients with kidney disease and demonstrate that azvudine could reduce the risk of all‐cause death without significant adverse events based on a large‐scale, multicenter, retrospective cohort study.</jats:p>",
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