Abdelrahman Zeinab, Liu Qian, Jiang Shanmei, Li Mengyuan, Sun Qingrong, Zhang Yue, Wang Xiaosheng
Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Big Data Research Institute, China Pharmaceutical University, Nanjing, China.
Front Pharmacol. 2021 Mar 15;12:607408. doi: 10.3389/fphar.2021.607408. eCollection 2021.
Limited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern. To estimate the efficacy and safety of COVID-19 therapeutics, we performed meta-analyses of the studies reporting clinical features and treatments of COVID-19 published from January 21 to September 6, 2020. We included 136 studies that involved 102,345 COVID-19 patients. The most prevalent treatments were antibiotics (proportion: 0.59, 95% CI: [0.51, 0.67]) and antivirals (proportion: 0.52, 95% CI: [0.44, 0.60]). The combination of lopinavir/ritonavir and Arbidol was the most effective in treating COVID-19 (standardized mean difference (SMD) = 0.68, 95% CI: [0.15, 1.21]). The use of corticosteroids was associated with a small clinical improvement (SMD = -0.40, 95% CI: [-0.85, -0.23]), but with a higher risk of disease progression and death (mortality: RR = 9.26, 95% CI: [4.81, 17.80]; hospitalization length: RR = 1.54, 95% CI: [1.39, 1.72]; severe adverse events: RR = 2.65, 95% CI: [2.09, 3.37]). The use of hydroxychloroquine was associated with a higher risk of death (RR = 1.68, 95% CI: [1.18, 2.38]). The combination of lopinavir/ritonavir, ribavirin, and interferon-β (RR = 0.34, 95% CI: [0.22, 0.54]); hydroxychloroquine (RR = 0.58, 95% CI: [0.39, 0.58]); and lopinavir/ritonavir (RR = 0.72, 95% CI: [0.56, 0.91]) was associated with reduced hospitalization length. Hydrocortisone (RR = 0.05, 95% CI: [0.03, 0.10]) and remdesivir (RR = 0.74, 95% CI: [0.62, 0.90]) were associated with lower incidence of severe adverse events. Dexamethasone was not significant in reducing disease progression (RR = 0.45, 95% CI: [0.16, 1.25]) and mortality (RR = 0.90, 95% CI: [0.70, 1.16]). The estimated combination of corticosteroids with antivirals was associated with a better clinical improvement than antivirals alone (SMD = -1.09, 95% CI: [-1.64, -0.53]). Antivirals are safe and effective in COVID-19 treatment. Remdesivir cannot significantly reduce COVID-19 mortality and hospitalization length, while it is associated with a lower incidence of severe adverse events. Corticosteroids could increase COVID-19 severity, but it could be beneficial when combined with antivirals. Our data are potentially valuable for the clinical treatment and management of COVID-19 patients.
目前应用的新型冠状病毒肺炎（COVID-19）治疗方法的疗效和安全性数据有限，及其对COVID-19结局的影响引发了更多关注。为评估COVID-19治疗方法的疗效和安全性，我们对2020年1月21日至9月6日发表的报告COVID-19临床特征和治疗方法的研究进行了荟萃分析。我们纳入了136项涉及102345例COVID-19患者的研究。最常用的治疗方法是抗生素（比例：0.59，95%置信区间：[0.51, 0.67]）和抗病毒药物（比例：0.52，95%置信区间：[0.44, 0.60]）。洛匹那韦/利托那韦与阿比多尔联合使用在治疗COVID-19方面最有效（标准化均数差（SMD）=0.68，95%置信区间：[0.15, 1.21]）。使用糖皮质激素与临床有小幅改善相关（SMD=-0.40，95%置信区间：[-0.85, -0.23]），但疾病进展和死亡风险更高（死亡率：相对危险度（RR）=9.26，95%置信区间：[4.81, 17.80]；住院时长：RR=1.54，95%置信区间：[1.39, 1.72]；严重不良事件：RR=2.65，95%置信区间：[2.09, 3.37]）。使用羟氯喹啉与死亡风险更高相关（RR=1.68，95%置信区间：[1.18, 2.38]）。洛匹那韦/利托那韦、利巴韦林和干扰素-β联合使用（RR=0.34，95%置信区间：[0.22, 0.54]）；羟氯喹啉（RR=0.58，95%置信区间：[0.39, 0.58]）；以及洛匹那韦/利托那韦（RR=0.72，95%置信区间：[0.56, 0.91]）与住院时长缩短相关。氢化可的松（RR=0.05，95%置信区间：[0.03, 0.10]）和瑞德西韦（RR=0.74，95%置信区间：[0.62, 0.90]）与严重不良事件发生率较低相关。地塞米松在降低疾病进展（RR=0.45，95%置信区间：[0.16, 1.25]）和死亡率（RR=0.90，95%置信区间：[0.70, 1.16]）方面无显著意义。估计糖皮质激素与抗病毒药物联合使用比单独使用抗病毒药物临床改善更好（SMD=-1.09，95%置信区间：[-1.64, -0.53]）。抗病毒药物在COVID-19治疗中安全有效。瑞德西韦不能显著降低COVID-19死亡率和住院时长，但其与严重不良事件发生率较低相关。糖皮质激素可能会增加COVID-19的严重程度，但与抗病毒药物联合使用时可能有益。我们的数据对COVID-19患者的临床治疗和管理可能具有重要价值。
