Commentary: A multicenter, real-world cohort study: effectiveness and safety of Azvudine in hospitalized COVID-19 patients with pre-existing diabetes

and safety of Azvudine in hospitalized COVID-19 patients with pre-existing diabetes. [1] 21 This multicenter real-world study represents a valuable contribution to the evolving 22 evidence base on antiviral use in high-risk populations. However, several 23 methodological limitations merit attention to better contextualize the findings and guide 24 future research. We wish to offer the following observations. 25 First, while the application of Kaplan-Meier and Cox proportional hazards 26 regression for time-to-event outcomes is methodologically sound, the analysis does not 27 adequately account for competing risks. Specifically, discharge alive represents a strong 28 competing event that may informatively censor the outcome of in-hospital mortality.The use of cumulative incidence functions and the Fine-Gray model would provide 30 more accurate estimates of absolute risk and avoid potential overestimation of mortality 31 probabilities. [2] Additionally, the definition of Azvudine exposure as a time-fixed 32 covariate from admission may introduce immortal time bias, as patients must survive long enough to receive treatment. The analysis does not report the distribution of time 34 from hospital admission to first administration, and immortal time bias cannot be ruled 35 out. Modeling treatment as a time-varying covariate or applying a landmark analysis 36 would help mitigate this bias.Second, the authors have commendably adjusted for numerous clinical covariates 38 and used propensity score matching to balance baseline characteristics. [1] Nevertheless,