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At present, there are some randomized controlled trials (RCTs) of oral small molecule drugs. The purpose of this study was to evaluate the efficacy and safety of oral small molecule drug treatment for COVID-19. RCTs were identified through systematic searches of PubMed, Embase, and Cochrane Central Register of Controlled Trials through 1 April 2023. A total of nine RCTs were included, including 30,970 COVID-19 patients comparing five treatments (azvudine, molnupiravir, paxlovid, VV116, and placebo). The Cochrane risk of bias tool for randomized trials (RoB) was used to assess the bias risk of the included studies. The direct and indirect evidence were combined using a Bayesian network meta-analysis (PROSPERO Code No: CRD42023397837). Direct analysis showed that paxlovid was associated with a reduced risk of mortality (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.06–0.25) and hospitalization (OR = 0.04, 95% CI: 0.00–0.67) compared with placebo. Network meta-analysis showed that paxlovid had the highest probability of being the best management strategy in patients with COVID-19, reducing mortality (OR = 0.11, 95% CI: 0.01–1.99; surface under the cumulative ranking curve [SUCRA]: 0.77) and hospitalization (OR = 0.06, 95% CI: 0.00–1.03; SUCRA: 0.95). For prespecified safety outcomes, SUCRA values ranked VV116 (OR = 0.09, 95% CI: 0.00–2.07: SUCRA 0.86) as the most beneficial intervention for the prevention of serious adverse events. When compared to other antiviral medications, paxlovid can reduce the mortality and hospitalization of COVID-19 patients.

Evaluation of oral small molecule drugs for the treatment of COVID-19 patients: a systematic review and network meta-analysis