Systemic corticosteroids and mortality in severe and critical COVID-19 patients in Wuhan, China

Background: Systemic corticosteroids are now recommended in many treatment
guidelines, though supporting evidence is limited to one randomised
controlled clinical trial (RECOVERY).  Objective: To identify
whether corticosteroids were beneficial to COVID-19 patients. 
Methods: 1514 severe and 249 critical hospitalized COVID-19 patients from
two medical centers in Wuhan, China. Multivariable Cox models, Cox model
with time-varying exposure and propensity score analysis
(inverse-probability-of-treatment-weighting (IPTW) and propensity score
matching (PSM)) to estimate the association of corticosteroid use with
risk of in-hospital mortality in severe and critical cases. Results:
Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%)
critical patients. Compared to non-corticosteroid group, systemic
corticosteroid use was not associated with beneficial effect in reducing
in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89,
p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028).
Findings were similar in time-varying Cox analysis. For severe COVID-19
patients at admission, corticosteroid use was not associated with improved
or harmful outcome in either PSM or IPTW analysis. For critical COVID-19
patients at admission, results were consistent with multivariable Cox
model analysis. Conclusion: Corticosteroid use was not associated with
beneficial effect in reducing in-hospital mortality for severe or critical
cases in Wuhan. Absence of the beneficial effect in our study in contrast
to that was observed in the RECOVERY clinical trial may be due to biases
in observational data, in particular prescription by indication bias,
differences in clinical characteristics of patients, choice of
corticosteroid used, timing of initiation of treatment and duration of
treatment.

背景：目前全身用糖皮质激素已被多项临床治疗指南推荐，尽管其支持证据仅来自一项随机对照临床试验（RECOVERY）。
目的：明确全身用糖皮质激素对新型冠状病毒肺炎（COVID-19）患者是否具有临床获益效果。
方法：纳入中国武汉两家医疗中心的1514例重型及249例危重型住院COVID-19患者。采用多变量Cox模型、含时变暴露的Cox模型以及倾向得分分析（包括逆概率治疗加权法（inverse-probability-of-treatment-weighting, IPTW）和倾向得分匹配法（propensity score matching, PSM）），评估重型与危重型患者使用糖皮质激素与院内死亡风险的关联。
结果：531例（35.1%）重型患者及159例（63.9%）危重型患者接受了全身糖皮质激素治疗。与未使用糖皮质激素的患者相比，全身糖皮质激素的使用并未使重型患者（HR=1.77，95%CI: 1.08~2.89，p=0.023）或危重型患者（HR=2.07，95%CI: 1.08~3.98，p=0.028）的院内死亡风险降低，未观察到获益效果。时变Cox模型分析结果与之一致。对于入院时即为重型的COVID-19患者，无论采用倾向得分匹配还是逆概率治疗加权分析，糖皮质激素的使用均未带来转归改善或不良影响。对于入院时即为危重型的COVID-19患者，分析结果与多变量Cox模型分析结果一致。
结论：在武汉地区的重型或危重型COVID-19患者中，全身用糖皮质激素的使用并未降低其院内死亡风险，未观察到获益效果。本研究未观测到获益效果，与RECOVERY临床试验的结果存在差异，这可能与观察性研究存在的偏倚有关，尤其是指征性处方偏倚，还可能与患者临床特征差异、所选糖皮质激素种类、治疗启动时机以及治疗疗程不同相关。