Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States of America.
Department of Integrative Biology, The University of Texas at Austin, Austin, Texas, United States of America.
PLoS One. 2024 Mar 21;19(3):e0294892. doi: 10.1371/journal.pone.0294892. eCollection 2024.
Dexamethasone was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial, but evidence is still needed to support its real-world effectiveness in heterogeneous populations of patients with a wide range of comorbidities.
COVID-19 inpatients represented within the National COVID Cohort Collaborative (N3C) Data Enclave, prior to vaccine availability, were studied. Primary outcome was in-hospital death; secondary outcome was combined in-hospital death and severe outcome defined by use of ECMO or mechanical ventilation. Missing data were imputed with single imputation. Dexamethasone-treated patients were propensity score (PS) matched to non-dexamethasone-treated controls, stratified by remdesivir treatment and based on demographics, baseline laboratory values, comorbidities, and amount of missing data before imputation. Treatment benefit was quantified using logistic regression. Further sensitivity analyses were performed using clinical adjusters in matched groups and in strata defined by quartiles of PS.
Dexamethasone treatment was associated with reduced risk of in-hospital mortality for n = 1,263 treated, matched 1:3 to untreated, patients not receiving remdesivir (OR = 0.77, 95% CI: 0.62 to 0.95, p = 0.017), and for n = 804 treated, matched 1:1 to untreated, patients receiving remdesivir (OR = 0.74, 95% CI: 0.53 to 1.02, p = 0.054). Treatment showed secondary outcome benefit. In sensitivity analyses, treatment effect generally remained similar with some heterogeneity of benefit across quartiles of PS, possibly reflecting concentration of benefit among the more severely affected.
We add evidence that dexamethasone provides benefit with respect to mortality and severe outcomes in a diverse, national hospitalized sample, prior to vaccine availability.
在大流行早期，基于 RECOVERY 试验，地塞米松被批准用于住院的 COVID-19 患者，但仍需要证据支持其在具有广泛合并症的患者异质人群中的真实世界疗效。
在疫苗可用之前，研究了全国 COVID 队列协作（N3C）数据飞地内的 COVID-19 住院患者。主要结局是院内死亡；次要结局是联合院内死亡和严重结局，定义为使用 ECMO 或机械通气。使用单一插补法对缺失数据进行插补。地塞米松治疗患者与非地塞米松治疗对照进行倾向评分（PS）匹配，按瑞德西韦治疗分层，并基于人口统计学、基线实验室值、合并症和插补前缺失数据量进行分层。使用逻辑回归量化治疗益处。在匹配组和按 PS 四分位数定义的分层中使用临床调整器进行了进一步的敏感性分析。
对于未接受瑞德西韦治疗的 n = 1,263 例接受治疗并匹配 3 倍未治疗的患者（OR = 0.77，95%CI：0.62 至 0.95，p = 0.017）和接受瑞德西韦治疗的 n = 804 例接受治疗并匹配 1:1 未治疗的患者（OR = 0.74，95%CI：0.53 至 1.02，p = 0.054），地塞米松治疗与住院死亡率降低相关。在敏感性分析中，治疗效果通常保持相似，PS 四分位数之间的益处存在一定的异质性，这可能反映了受益人群集中在病情更严重的人群中。
我们提供了在疫苗可用之前，地塞米松在多样化的全国住院患者样本中提供死亡率和严重结局益处的证据。
