Background and importance 

mRNA-based host response signatures have been reported to improve sepsis diagnostics. Meanwhile, prognostic markers for the rapid and accurate prediction of severity in patients with suspected acute infections and sepsis remain an unmet need. IMX-SEV-2 is a 29-host-mRNA classifier designed to predict disease severity in patients with acute infection or sepsis.

Objective 

Validation of the host-mRNA infection severity classifier IMX-SEV-2.

Design, settings and participants 

Prospective, observational, convenience cohort of emergency department (ED) patients with suspected acute infections.

Outcome measures and analysis 

Whole blood RNA tubes were analyzed using independently trained and validated composite target genes (IMX-SEV-2). IMX-SEV-2-generated risk scores for severity were compared to the patient outcomes in-hospital mortality and 72-h multiorgan failure.

Main results 

Of the 312 eligible patients, 22 (7.1%) died in hospital and 58 (18.6%) experienced multiorgan failure within 72 h of presentation. For predicting in-hospital mortality, IMX-SEV-2 had a significantly higher area under the receiver operating characteristic (AUROC) of 0.84 [95% confidence intervals (CI), 0.76–0.93] compared to 0.76 (0.64–0.87) for lactate, 0.68 (0.57–0.79) for quick Sequential Organ Failure Assessment (qSOFA) and 0.75 (0.65–0.85) for National Early Warning Score 2 (NEWS2), (P = 0.015, 0.001 and 0.013, respectively). For identifying and predicting 72-h multiorgan failure, the AUROC of IMX-SEV-2 was 0.76 (0.68–0.83), not significantly different from lactate (0.73, 0.65–0.81), qSOFA (0.77, 0.70–0.83) or NEWS2 (0.81, 0.75–0.86).

Conclusion 

The IMX-SEV-2 classifier showed a superior prediction of in-hospital mortality compared to biomarkers and clinical scores among ED patients with suspected infections. No improvement for predicting multiorgan failure was found compared to established scores or biomarkers. Identifying patients with a high risk of mortality or multiorgan failure may improve patient outcomes, resource utilization and guide therapy decision-making.

中文翻译：

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在急诊科疑似急性感染和脓毒症患者中转录组学严重程度分类器的前瞻性验证

背景和重要性 

据报道，基于 mRNA 的宿主反应特征可改善败血症诊断。同时，用于快速准确预测疑似急性感染和败血症患者严重程度的预后标志物仍未得到满足。IMX-SEV-2 是一种包含 29 个宿主 mRNA 的分类器，旨在预测急性感染或败血症患者的疾病严重程度。

客观的 

宿主 mRNA 感染严重程度分类器 IMX-SEV-2 的验证。

设计、设置和参与者 

疑似急性感染的急诊科 (ED) 患者的前瞻性、观察性、便利队列。

结果测量和分析 

使用独立训练和验证的复合靶基因 (IMX-SEV-2) 分析全血 RNA 管。将 IMX-SEV-2 生成的严重性风险评分与院内死亡率和 72 小时多器官衰竭患者结果进行比较。

主要结果 

在 312 名符合条件的患者中，22 名 (7.1%) 死于医院，58 名 (18.6%) 在就诊后 72 小时内出现多器官衰竭。对于预测院内死亡率，IMX-SEV-2 的接受者操作特征 (AUROC) 下的面积显着更高，为 0.84 [95% 置信区间 (CI)，0.76–0.93]，而乳酸为 0.76 (0.64–0.87) , 快速序贯器官衰竭评估 (qSOFA) 为 0.68 (0.57–0.79)，国家早期预警评分 2 (NEWS2) 为 0.75 (0.65–0.85)，（分别为P  = 0.015、0.001 和 0.013）。对于识别和预测 72 小时多器官衰竭，IMX-SEV-2 的 AUROC 为 0.76 (0.68–0.83)，与乳酸 (0.73, 0.65–0.81)、qSOFA (0.77, 0.70–0.83) 或 NEWS2 ( 0.81、0.75–0.86）。

结论 

与疑似感染的 ED 患者的生物标志物和临床评分相比，IMX-SEV-2 分类器显示出对院内死亡率的更好预测。与已建立的分数或生物标志物相比，没有发现预测多器官衰竭的改进。识别具有高死亡率或多器官衰竭风险的患者可能会改善患者预后、资源利用率并指导治疗决策。