Sarah Cannon, Nashville, Tennessee, USA.
HCA Healthcare, HCA Research Institute (HRI), Nashville, Tennessee, USA.
J Clin Invest. 2021 Oct 15;131(20). doi: 10.1172/JCI151788.
BACKGROUNDEvidence supporting convalescent plasma (CP), one of the first investigational treatments for coronavirus disease 2019 (COVID-19), has been inconclusive, leading to conflicting recommendations. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19.METHODSThe multicenter, electronic health records-based, retrospective study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare-affiliated community hospitals. Coarsened exact matching (1:k) was employed, resulting in a sample of 3774 CP and 10,687 comparison patients.RESULTSExamination of mortality using a shared frailty model, controlling for concomitant medications, date of admission, and days from admission to transfusion, demonstrated a significant association of CP with lower mortality risk relative to the comparison group (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.59-0.86; P < 0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our real-time risk model (RTRM), indicated that patients who received CP recovered more quickly. The stratification of days to transfusion revealed that CP within 3 days after admission, but not within 4 to 7 days, was associated with a significantly lower mortality risk (aHR = 0.53; 95% CI, 0.47-0.60; P < 0.001). CP serology level was inversely associated with mortality when controlling for its interaction with days to transfusion (HR = 0.998; 95% CI, 0.997-0.999; P = 0.013), yet it did not reach univariable significance.CONCLUSIONSThis large, diverse, multicenter cohort study demonstrated that CP, compared with matched controls, is significantly associated with reduced risk of in-hospital mortality. These observations highlight the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19.FUNDINGThis research was supported in whole by HCA Healthcare and/or an HCA Healthcare-affiliated entity, including Sarah Cannon and Genospace.
背景
支持恢复期血浆(CP)的证据尚无定论,这使得 CP 成为治疗 2019 年冠状病毒病(COVID-19)的首批研究性治疗方法之一,导致推荐意见相互矛盾。主要目的是对 CP 治疗 COVID-19 患者全因住院死亡率进行一项比较有效性研究。
方法
这项多中心、基于电子病历的回顾性研究纳入了 176 家 HCA 医疗保健附属社区医院中 44770 例 COVID-19 住院患者。采用粗化精确匹配(1:k),得到 3774 例 CP 患者和 10687 例对照患者的样本。
结果
使用共享脆弱性模型检查死亡率,同时控制伴随药物、入院日期和从入院到输血的天数,结果显示 CP 与对照组相比,死亡率风险显著降低(校正后的危险比[aHR] = 0.71;95%置信区间,0.59-0.86;P < 0.001)。通过我们的实时风险模型(RTRM)中 400 个临床人口统计学特征代表的患者风险轨迹检查表明,接受 CP 的患者恢复得更快。输血天数的分层表明,入院后 3 天内接受 CP,而不是 4 至 7 天内接受 CP,与死亡率风险显著降低相关(aHR = 0.53;95%置信区间,0.47-0.60;P < 0.001)。在控制 CP 与输血天数的相互作用后,CP 血清学水平与死亡率呈负相关(HR = 0.998;95%置信区间,0.997-0.999;P = 0.013),但未达到单变量显著性。
结论
这项大型、多样化、多中心队列研究表明,与匹配对照相比,CP 显著降低了住院死亡率风险。这些观察结果强调了真实世界证据的实用性,并表明在放弃 CP 作为 COVID-19 可行治疗方法之前,需要进一步评估。
资助
这项研究完全由 HCA 医疗保健公司及其附属实体(包括 Sarah Cannon 和 Genospace)资助。