Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study
Abstract Azvudine and nirmatrelvir-ritonavir (Paxlovid) were widely used to treat patients with COVID-19 in China during the Omicron wave. However, the efficacy and safety of azvudine versus Paxlovid are poorly established. This study included 40,876 hospitalized patients with COVID-19 from eleven h...
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Nature Publishing Group
2025-01-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02126-w |
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| author | Haiyu Wang Guangying Cui Ming Cheng Tuerganaili Aji Guotao Li Xinjun Hu Guangming Li Shixi Zhang Yanyang Zhang Linqi Diao Pan Li Ling Wang Yiqiang Yuan Guowu Qian Ruiqing Zhang Xiaoli Jin Juan Wang Hong Luo Donghua Zhang Mingming Wang Silin Li Zhan Song Mengzhao Yang Guanyue Su Ranran Sun Junbiao Chang Zujiang Yu Zhigang Ren |
| author_facet | Haiyu Wang Guangying Cui Ming Cheng Tuerganaili Aji Guotao Li Xinjun Hu Guangming Li Shixi Zhang Yanyang Zhang Linqi Diao Pan Li Ling Wang Yiqiang Yuan Guowu Qian Ruiqing Zhang Xiaoli Jin Juan Wang Hong Luo Donghua Zhang Mingming Wang Silin Li Zhan Song Mengzhao Yang Guanyue Su Ranran Sun Junbiao Chang Zujiang Yu Zhigang Ren |
| author_sort | Haiyu Wang |
| collection | DOAJ |
| description | Abstract Azvudine and nirmatrelvir-ritonavir (Paxlovid) were widely used to treat patients with COVID-19 in China during the Omicron wave. However, the efficacy and safety of azvudine versus Paxlovid are poorly established. This study included 40,876 hospitalized patients with COVID-19 from eleven hospitals in Henan and Xinjiang Provinces, China. Clinical outcomes were compared between the two drugs via Kaplan–Meier analysis and Cox regression models. Additionally, in vitro and in vivo experiments were used to evaluate the antitumor effects and safety of both drugs. Single-cell RNA sequencing was performed to elucidate the tumor immune landscape after azvudine treatment. After propensity score matching, 2404 azvudine and 1202 Paxlovid recipients from Henan Province were included. Cox regression revealed that azvudine was related to an 18% lower risk of all-cause death than Paxlovid (95% CI: 0.676–0.987), was not obviously different in composite disease progression. The robustness of the findings was verified by the Xinjiang cohort and three sensitivity analyses. Fewer adverse events were observed in the azvudine group. Subgroup analysis revealed that azvudine provided greater benefits for patients with malignant tumors, significantly reducing both all-cause death (hazard ratio [HR]: 0.33, 95% CI: 0.20−0.54) and composite disease progression (HR: 0.54, 95% CI: 0.33−0.88). Furthermore, azvudine can suppress the growth of hepatocellular carcinoma (HCC) by regulating CD4+ T and CD8+ T cells in vivo. These findings suggest that azvudine therapy is not inferior to Paxlovid in hospitalized COVID-19 patients and has fewer adverse effects. Notably, azvudine may offer greater clinical benefit for patients with HCC. |
| format | Article |
| id | doaj-art-3728d79c1bd14148a8efcc7a1c14d32a |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
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| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-3728d79c1bd14148a8efcc7a1c14d32a2025-01-19T12:40:29ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-01-0110111410.1038/s41392-025-02126-wReal‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort studyHaiyu Wang0Guangying Cui1Ming Cheng2Tuerganaili Aji3Guotao Li4Xinjun Hu5Guangming Li6Shixi Zhang7Yanyang Zhang8Linqi Diao9Pan Li10Ling Wang11Yiqiang Yuan12Guowu Qian13Ruiqing Zhang14Xiaoli Jin15Juan Wang16Hong Luo17Donghua Zhang18Mingming Wang19Silin Li20Zhan Song21Mengzhao Yang22Guanyue Su23Ranran Sun24Junbiao Chang25Zujiang Yu26Zhigang Ren27Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical Information, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Infectious Diseases, Luoyang Central Hospital Affiliated of Zhengzhou UniversityDepartment of Infectious Diseases, the First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and TechnologyDepartment of Liver Disease, the Affiliated Infectious Disease Hospital of Zhengzhou UniversityDepartment of Infectious Diseases, Shangqiu Municipal HospitalHenan Center for Disease Control and PreventionHenan Center for Disease Control and PreventionDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiovascular Medicine, Henan Provincial Chest Hospital Affiliated of Zhengzhou UniversityDepartment of Cardiovascular Medicine, Henan Provincial Chest Hospital Affiliated of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, Nanyang Central HospitalDepartment of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Infectious Diseases, Luoyang Central Hospital Affiliated of Zhengzhou UniversityDepartment of Liver Disease, the Affiliated Infectious Disease Hospital of Zhengzhou UniversityGuangshan County People’s Hospital, Guangshan CountyDepartment of Infectious Diseases, Anyang City Fifth People’s HospitalDepartment of Infectious Diseases, Shangqiu Municipal HospitalDepartment of Respiratory and Critical Care Medicine, Fengqiu County People’s HospitalDepartment of Gastrointestinal Surgery, Nanyang Central HospitalDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou UniversityState Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Zhengzhou UniversityDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou UniversityAbstract Azvudine and nirmatrelvir-ritonavir (Paxlovid) were widely used to treat patients with COVID-19 in China during the Omicron wave. However, the efficacy and safety of azvudine versus Paxlovid are poorly established. This study included 40,876 hospitalized patients with COVID-19 from eleven hospitals in Henan and Xinjiang Provinces, China. Clinical outcomes were compared between the two drugs via Kaplan–Meier analysis and Cox regression models. Additionally, in vitro and in vivo experiments were used to evaluate the antitumor effects and safety of both drugs. Single-cell RNA sequencing was performed to elucidate the tumor immune landscape after azvudine treatment. After propensity score matching, 2404 azvudine and 1202 Paxlovid recipients from Henan Province were included. Cox regression revealed that azvudine was related to an 18% lower risk of all-cause death than Paxlovid (95% CI: 0.676–0.987), was not obviously different in composite disease progression. The robustness of the findings was verified by the Xinjiang cohort and three sensitivity analyses. Fewer adverse events were observed in the azvudine group. Subgroup analysis revealed that azvudine provided greater benefits for patients with malignant tumors, significantly reducing both all-cause death (hazard ratio [HR]: 0.33, 95% CI: 0.20−0.54) and composite disease progression (HR: 0.54, 95% CI: 0.33−0.88). Furthermore, azvudine can suppress the growth of hepatocellular carcinoma (HCC) by regulating CD4+ T and CD8+ T cells in vivo. These findings suggest that azvudine therapy is not inferior to Paxlovid in hospitalized COVID-19 patients and has fewer adverse effects. Notably, azvudine may offer greater clinical benefit for patients with HCC.https://doi.org/10.1038/s41392-025-02126-w |
| spellingShingle | Haiyu Wang Guangying Cui Ming Cheng Tuerganaili Aji Guotao Li Xinjun Hu Guangming Li Shixi Zhang Yanyang Zhang Linqi Diao Pan Li Ling Wang Yiqiang Yuan Guowu Qian Ruiqing Zhang Xiaoli Jin Juan Wang Hong Luo Donghua Zhang Mingming Wang Silin Li Zhan Song Mengzhao Yang Guanyue Su Ranran Sun Junbiao Chang Zujiang Yu Zhigang Ren Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study Signal Transduction and Targeted Therapy |
| title | Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study |
| title_full | Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study |
| title_fullStr | Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study |
| title_full_unstemmed | Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study |
| title_short | Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study |
| title_sort | real world effectiveness and safety of oral azvudine versus nirmatrelvir ritonavir paxlovid in hospitalized patients with covid 19 a multicenter retrospective cohort study |
| url | https://doi.org/10.1038/s41392-025-02126-w |
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