英国布里斯托大学Jonathan A. C. Sterne团队研究了全身性皮质类固醇治疗COVID-19重症患者与死亡率的关系。2020年9月2日，该研究发表在《美国医学会杂志》上。

临床试验数据表明，低剂量地塞米松可降低需要呼吸支持的住院COVID-19患者的死亡率。

为了评估使用皮质类固醇和常规治疗或安慰剂与28天全因死亡率之间的相关性，研究组进行了一项前瞻性荟萃分析，汇集了7项随机临床试验的数据。2020年2月26日至6月9日，这7项试验在12个国家招募了1703例COVID-19重症患者，将其随机分组，其中678例接受全身性地塞米松、氢化可的松或甲基强的松治疗，1025例接受常规治疗或安慰剂。主要结局为28天的全因死亡率。

1703例患者的中位年龄为60岁，其中29%为女性。由于随机方法，7项死亡率结果中有6项偏倚风险被评估为“低”，1项被评估为“略相关”。5项试验报告了28天死亡率，1项试验报告了21天死亡率，1项试验报告了30天死亡率。皮质类固醇组中有222人死亡，常规治疗或护理组中有425人死亡，组间差异显著。

根据随机效应荟萃分析，试验结果之间几乎没有矛盾，总OR为0.70。与常规治疗或安慰剂相比，地塞米松与死亡率相关的固定效应总OR为0.64，氢化可的松为0.69，甲基强的松龙为0.91。皮质类固醇组354例患者中发生了64例严重不良事件，常规治疗或安慰剂组342例患者中有80例。

总之，全身性皮质类固醇治疗COVID-19重症患者，与常规护理或安慰剂相比，可显著降低28天的全因死亡率。

附：英文原文

Title: Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis

Author: The WHO Rapid Evidence Appraisal for COVID- Therapies (REACT) Working Group, Jonathan A. C. Sterne, Srinivas Murthy, Janet V. Diaz, Arthur S. Slutsky, Jesús Villar, Derek C. Angus, Djillali Annane, Luciano Cesar Pontes Azevedo, Otavio Berwanger, Alexandre B. Cavalcanti, Pierre-Francois Dequin, Bin Du, Jonathan Emberson, David Fisher, Bruno Giraudeau, Anthony C. Gordon, Anders Granholm, Cameron Green, Richard Haynes, Nicholas Heming, Julian P. T. Higgins, Peter Horby, Peter Jüni, Martin J. Landray, Amelie Le Gouge, Marie Leclerc, Wei Shen Lim, Flávia R. Machado, Colin McArthur, Ferhat Meziani, Morten Hylander Mller, Anders Perner, Marie Warrer Petersen, Jelena Savovi, Bruno Tomazini, Viviane C. Veiga, Steve Webb, John C. Marshall

Issue&Volume: 2020-09-02

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.

DOI: 10.1001/jama.2020.17023

Source: https://jamanetwork.com/journals/jama/fullarticle/2770279