| Summary: | Haoshuang Liu,1,2 Jingfeng Chen,1,2 Weihao Shao,3 Su Yan,1,2 Suying Ding1,2 1Health Management Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2College of Public Health, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 3School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Suying Ding, Department of Health Management Center, the First Affiliated Hospital of Zhengzhou University, Longhu Zhonghuan Road, Jinshui District, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 158 3802 3097, Email fccdingsy@zzu.edu.cnObjective: Numerous pharmacological interventions are now under investigation for the treatment of the 2019 coronavirus pandemic (COVID-19), and the evidence is rapidly evolving. Our aim is to evaluate the comparative efficacy and safety of these drugs.Methods: We searched for randomized clinical trials (RCTs) on the efficacy and safety of novel oral antivirals for the treatment of hospitalized COVID-19 patients until November 30, 2022, including baricitinib, ivermectin (IVM), favipiravir (FVP), chloroquine (CQ), lopinavir and ritonavir (LPV/RTV), hydroxychloroquine (HCQ), and hydroxychloroquine plus azithromycin (HCQ+AZT). The main outcomes of this network meta-analysis (NMA) were in-hospital mortality, adverse event (AE), recovery time, and improvement in peripheral capillary oxygen saturation (SpO2). For dichotomous results, the odds ratio (OR) was used, and the 95% confidence interval (CI) was determined. We also used meta-regression to explore whether different treatments affected efficacy and safety. STATA 15.0 was used to conduct the NMA. The research protocol was registered with PROSPERO (#CRD 42023415743).Results: Thirty-six RCTs, with 33,555 hospitalized COVID-19 patients, were included in this analysis. First, we compared the efficacy of different novel oral antivirals. Baricitinib (OR 0.56, 95% CI: 0.35 to 0.90) showed the highest probability of being the optimal probiotic species in reducing in-hospital mortality and suggested that none of the interventions reduced AE better than placebo. In terms of safety outcomes, IVM ranked first in improving the recovery time of hospitalized COVID-19 patients (mean difference (MD) − 1.36, 95% CI: − 2.32 to − 0.39). In addition, patients were most likely to increase SpO2 (OR 1.77, 95% CI: 0.09 to 3.45). The meta-regression revealed no significant differences between participants using different novel oral antivirals in all outcomes in hospitalized COVID-19 patients.Conclusion: Currently, baricitinib has reduced in-hospital mortality in hospitalized COVID-19 patients, with moderate certainty of evidence. IVM appeared to be a safer option than placebo in improving recovery time, while FVP was associated with increased SpO2 safety outcomes. These preliminary evidence-based observations should guide clinical practice until more data are made public.Keywords: COVID-19, network meta-analysis, pharmacological intervention, efficacy, safety
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