Effectiveness of azvudine against severe outcomes among hospitalized COVID-19 patients in Xinjiang, China: a single-center, retrospective, matched cohort study

ABSTRACT

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.

KEYWORDS:

• Antiviral therapy
• azvudine
• all-cause death
• hospitalized
• Omicron variant

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

We thank all participants in this study for their cooperation in disease surveillance and control measures. We also thank healthcare professionals, caregiver partners, and public health practitioners for their contributions to the community.

Author contributions

Conceptualization: Shi Zhao, and Kai Wang. Methodology: Shi Zhao, Zihao Guo, and Kai Wang. Software: Abiden Kapar, and Kai Wang. Validation: Abiden Kapar, Kailu Wang, Zihao Guo, Shi Zhao, and Kai Wang. Formal analysis: Abiden Kapar, Songsong Xie, and Kai Wang. Investigation: Abiden Kapar, Songsong Xie, Kailu Wang, and Kai Wang. Resources: Songsong Xie, and Kai Wang. Data Curation: Yan Nan, Yaling Du, and Xi Yin. Writing – Original Draft: Abiden Kapar, Songsong Xie, and Zihao Guo. Writing – Review and Editing: Tao Gong, Xiu Gu, Yang Zhou, Wenli Lu, Zhaohui Luo, Kailu Wang, Shi Zhao, and Kai Wang. Visualization: Kai Wang. Supervision: Shi Zhao, and Kai Wang. Project Administration: Abiden Kapar, and Kai Wang. Funding acquisition: Songsong Xie, and Kai Wang. All authors critically read the manuscript and gave final approval for publication.

Data availability statement

The original database containing confidential patient information cannot be made publicly available. The anonymized data used in this study were available based on reasonable request to the corresponding authors.

Ethics statement

The collection of specimens, epidemiological and clinical data for SARS-CoV-2 infected individuals and their close contacts is a part of a continuing public health investigation of COVID-19 outbreaks, ruled in the Protocol on the Prevention and Control of COVID-19 by the National Health Commission of the People’s Republic of China, which was exempt from ethical approval (i.e. institutional review board assessment). This study was approved by the institutional ethics committee of the First Affiliated Hospital of Shihezi University, where the study samples were recruited (IRB No.: KJ2023-294-01). Individual verbal consent was obtained when collecting personal information and human samples by governmental healthcare professionals in the field.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14787210.2024.2362900

Additional information

Funding

This study was supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2020-PT330-003], Guiding science and Technology Project of Xinjiang Production and Construction Corps [2022ZD026], the Youth science and technology innovation talent of Tianshan Talent Training Program in Xinjiang [Grant No.: 2022TSYCCX0099], and the 14-th Five-Year Plan Distinctive Program of Public Health and Preventive Medicine in Higher Education Institutions of Xinjiang Uygur Autonomous Region. SZ was supported by Tianjin Medical University start-up funding.