RESUMO
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).
RESUMO
BACKGROUND: To assess the applicability of the association between estimated glucose disposal rate (eGDR) and all-cause mortality in the elderly population, and the mediating role of brachial-ankle pulse wave velocity (baPWV). METHODS: This was a follow-up cohort study based on the cross-sectional survey of community-dwelling elderly. All participants in the study were included between September 2009 and June 2010, and the follow-up time was December 2020. Participants included 1862 Chinese community-dwelling elderly aged 60 years and above. Insulin resistance assessed by eGDR and arterial stiffness assessed by baPWV were the primary exposures of interest. Mortality, which was followed up until December 2020, was the primary outcome. Cox proportional hazards regression models were used to estimate the association of eGDR with mortality. The mediating effect of baPWV in this association was assessed by mediation analysis. RESULTS: A total of 1826 participants with a mean age of 71.03 years old were included in the study. During the median follow-up of 10.75 years, 334 participants died. The adjusted HR comparing the highest versus the lowest eGDR quartile was 0.22 (95% CI 0.09 to 0.54; p<0.001) in the Cox proportional hazards model. The results of mediation analysis showed that baPWV had a significant mediation impact on the link between eGDR and all-cause mortality both as continuous or categorical variables. CONCLUSION: eGDR is an independent predictor of all-cause mortality in the elderly population. baPWV partially mediated the association of eGDR and long-term all-cause mortality as a mediator factor.
