Is Azvudine Comparable to Nirmatrelvir-Ritonavir in Real-World Efficacy and Safety for Hospitalized Patients with COVID-19? A Retrospective Cohort Study.

INTRODUCTION: Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China. METHODS: This retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion (PNANC), time to first nucleic-acid negative conversion (TFNANC), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes. RESULTS: This study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56-3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78-3.60; P = 0.189), PNANC (HR 0.87; 95% CI 0.69-1.09; P = 0.220), length of stay (ß - 0.82; 95% CI - 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer TFNANC (ß 2.53; 95% CI 0.76-4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses. CONCLUSION: Azvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes.

Catalytic asymmetric multicomponent reactions of isocyanide, isothiocyanate and alkylidene malonates.

Several unique chiral 3,4-dihydro-2H-pyrrole-2-thiones were made readily available by carrying out, in each case, a chiral-Mg(OTf)2/N,N'-dioxide-complex-promoted formal [2+1+2] cycloaddition in the presence of tetraethylenediamine. Control experiments revealed that in situ-generated ammonium thiocyanate was crucial for maintaining high enantioselectivity through its inhibition of the HNCS-induced racemization of the products.