类固醇药物可拯救重症新冠患者的生命

诸平

据《新科学家》（New Scientist）杂志网站2020年9月2日报道，冠状病毒的最新新闻每天都会更新，包括冠状病毒的病例，来自《新科学家》最新消息莫过于专题报道和访谈以及有关covid-19大流行的基本信息。据约翰·霍普金斯大学（Johns Hopkins University）的数据，新冠病毒已经导致全球死亡人数已超过85.8万；确诊病例数超过2580万，尽管真实的病例数可能会更高。为了拯救更多人的生命，降低死亡率。疫苗研究和新药研发也在积极展开的同时，老药新用途的探索也在不断深入之中。《新科学家》2020年9月2日报道的减轻炎症的类固醇药物（Steroid drugs）可挽救严重的covid-19患者的生命就是老药新用途探索的一个例证。

已经证实一组减轻炎症的药物可以增加严重covid-19 患者的生存率。在一项具有里程碑意义的研究中，到目前为止已完成的所有研究都在研究类固醇对冠状病毒的作用，世界卫生组织（WHO）REACT工作组的研究人员分析了7项随机临床试验的结果，其中包括1703例重度新冠患者（covid-19）， 他们比较了接受3种皮质类固醇药物之一的患者的结果与那些接受标准护理或安慰剂的人的死亡率。3种皮质类固醇药物分别是地塞米松（dexamethasone），氢化可的松（hydrocortisone）和甲基强的松龙（methylprednisolone）。研究人员发现，接受皮质类固醇治疗的人28天后死于该病的患者比例为32％，而未接受皮质类固醇治疗的人中死于该病的比例为40％。

地塞米松（dexamethasone）        氢化可的松（hydrocortisone）

甲基强的松龙（methylprednisolone）

伦敦卫生与热带医学学院（London School of Hygiene and Tropical Medicine）的斯蒂芬·埃文斯（Stephen Evans）在一份声明中说：“地塞米松（dexamethasone）是最有益的证据。” 这些新结果2020年9月2日发表在《美国医学会杂志》（Journal of the American Medical Association, JAMA）——The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Article Information. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19A Meta-analysis. JAMA. Published online September 2, 2020. doi:10.1001/jama.2020.17023

此研究为RECOVERY试验的早期发现增加了分量，该试验发现地塞米松使重症covid-19患者的呼吸机死亡人数减少了1/3，而呼吸机患者减少了1/3。斯蒂芬·埃文斯说：“这项分析使人们更加相信地塞米松在重症covid-19患者中确实具有重要的作用。” 研究的结果是，预期世界卫生组织将更新其治疗指南。在英国，这种药物一直在使用 自2020年6月以来用于治疗重症covid-19患者。更多信息请注意浏览原文或者相关报道。

Key Points

Question  Is administration of systemic corticosteroids associated with reduced 28-day mortality in critically ill patients with coronavirus disease 2019 (COVID-19)?

Findings  In this prospective meta-analysis of 7 randomized trials that included 1703 patients of whom 647 died, 28-day all-cause mortality was lower among patients who received corticosteroids compared with those who received usual care or placebo (summary odds ratio, 0.66).

Meaning  Administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality in critically ill patients with COVID-19.

Abstract

Importance  Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.

Objective  To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality.

Design, Setting, and Participants  Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I² statistic. The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios.

Exposures  Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).

Main Outcomes and Measures  The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events.

Results  A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as “low” for 6 of the 7 mortality results and as “some concerns” in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I² = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo.

Conclusions and Relevance  In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.