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糖皮质激素治疗 COVID-19 的疗效和安全性:RCT 的系统评价和荟萃分析。

Efficacy and safety of glucocorticoids in the treatment of COVID-19: a systematic review and meta-analysis of RCTs.

机构信息

Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.

Institute of Respiratory Diseases of Sun Yat-sen University, No. 58, Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.

出版信息

Clin Exp Med. 2024 Jul 13;24(1):157. doi: 10.1007/s10238-024-01405-0.

Abstract

In the realm of acute respiratory infections, coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a global public health challenge. The application of corticosteroids (CSs) in COVID-19 remains a contentious topic among researchers. Accordingly, our team performed a comprehensive meta-analysis of randomized controlled trials (RCTs) to meticulously evaluate the safety and efficacy of CSs in hospitalized COVID-19 patients. To explore efficacy of CSs in the treatment of COVID-19 patients, we meticulously screened RCTs across key databases, including PubMed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, as well as China's CNKI and Wanfang Data. We focused on assessing the 28 days mortality rates. We evaluated the data heterogeneity using the Chi-square test and I values, setting significance at 0.1 and 50%. Data from 21 RCTs involving 5721 participants were analyzed. The analysis did not demonstrate a significant association between CSs intervention and the 28 days mortality risk in hospitalized COVID-19 patients (relative risk [RR] = 0.93; 95% confidence interval [95% CI]: 0.84-1.03; P = 0.15). However, subgroup analysis revealed a significant reduction in 28 days mortality among patients with moderate-to-severe COVID-19 (RR at 0.85; 95% CI: 0.76-0.95; P = 0.004). Specifically, short-term CS administration (≤ 3 days) was associated with a substantial improvement in clinical outcomes (RR = 0.24; 95% CI: 0.09-0.63; P = 0.004), as was longer-term use (≥ 8 days) (RR = 0.88; 95% CI: 0.77-0.99; P = 0.04). Additionally, in patients with moderate-to-severe COVID-19, the administration of dexamethasone increased the number of 28 days ventilator-free days (Mean Difference = 1.92; 95% CI: 0.44-3.40; P = 0.01). Methylprednisolone also demonstrated significant benefits in improving clinical outcomes (RR = 0.24; 95% CI: 0.09-0.63; P = 0.004). Our meta-analysis demonstrated that although there is no significant difference in 28 days mortality rates among hospitalized COVID-19 patients, the use of CSs may be beneficial in improving clinical outcomes in moderate or severe COVID-19 patients. There was no significant increase in the occurrence of adverse events associated with the use of CSs. Our meta-analysis provides evidence that while CSs may not be suitable for all COVID-19 patients, they could be effective and safe in severely ill COVID-19 patients. Consequently, it is recommended to administer CSs for personalized treatments in COVID-19 cases to improve the clinical outcomes while minimizing adverse events.

摘要

在急性呼吸道感染领域,由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的冠状病毒病-19(COVID-19)对全球公共卫生构成挑战。皮质类固醇(CSs)在 COVID-19 中的应用仍然是研究人员争论的话题。因此,我们的团队对随机对照试验(RCTs)进行了全面的荟萃分析,以仔细评估 CSs 在住院 COVID-19 患者中的安全性和疗效。为了探讨 CSs 在 COVID-19 患者治疗中的疗效,我们仔细筛选了包括 PubMed、Web of Science、Embase、Cochrane 图书馆、ClinicalTrials.gov 以及中国的 CNKI 和万方数据在内的关键数据库中的 RCTs。我们重点评估了 28 天死亡率。我们使用卡方检验和 I 值评估数据异质性,以 0.1 和 50%作为显著性水平。分析了 21 项涉及 5721 名参与者的 RCT。分析结果显示,CSs 干预与住院 COVID-19 患者 28 天死亡率之间无显著关联(相对风险 [RR] = 0.93;95%置信区间 [95%CI]:0.84-1.03;P = 0.15)。然而,亚组分析显示,中重度 COVID-19 患者的 28 天死亡率显著降低(RR 为 0.85;95%CI:0.76-0.95;P = 0.004)。具体来说,短期(≤3 天)CS 给药与临床结局显著改善相关(RR = 0.24;95%CI:0.09-0.63;P = 0.004),长期(≥8 天)使用也与临床结局显著改善相关(RR = 0.88;95%CI:0.77-0.99;P = 0.04)。此外,在中重度 COVID-19 患者中,地塞米松给药增加了 28 天无呼吸机天数(平均差值 = 1.92;95%CI:0.44-3.40;P = 0.01)。甲泼尼龙也显著改善了临床结局(RR = 0.24;95%CI:0.09-0.63;P = 0.004)。我们的荟萃分析表明,尽管住院 COVID-19 患者的 28 天死亡率之间无显著差异,但 CSs 的使用可能有助于改善中重度 COVID-19 患者的临床结局。CSs 的使用并未显著增加与不良反应相关的发生率。我们的荟萃分析提供了证据,表明虽然 CSs 可能不适合所有 COVID-19 患者,但它们在重症 COVID-19 患者中可能是有效且安全的。因此,建议在 COVID-19 病例中根据个体情况使用 CSs 进行治疗,以改善临床结局,同时最小化不良反应的发生。

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