In order to identify biomarkers for earlier prediction of COVID-19 outcome, we collected blood samples from patients with fatal outcomes (non-survivors) and with positive clinical outcomes (survivors) at ICU admission and after seven days. COVID-19 survivors and non-survivors showed significantly different transcript levels for 93 genes in whole blood already at ICU admission as revealed by RNA-Seq. These differences became even more pronounced at day 7, resulting in 290 differentially expressed genes. Many identified genes play a role in the differentiation of hematopoietic cells. For validation, we designed an RT-qPCR assay for C-type lectin domain family 12 member A (CLEC12A) and acetylcholinesterase (ACHE), two transcripts that showed highest potential to discriminate between survivors and non-survivors at both time points. Using our combined RT-qPCR assay we examined 33 samples to accurately predict patient survival with an AUROC curve of 0.931 (95% CI = 0.814–1.000) already at ICU admission. CLEC12A and ACHE showed improved prediction of patient outcomes compared to standard clinical biomarkers including CRP and PCT in combination (AUROC = 0.403, 95% CI = 0.108–0.697) or SOFA score (AUROC = 0.701 95% CI = 0.451–0.951) at day 0. Therefore, analyzing CLEC12A and ACHE gene expression from blood may provide a promising approach for early risk stratification of severely ill COVID-19 patients.

为了确定早期预测 COVID-19 结果的生物标志物，我们收集了入住 ICU 时和 7 天后出现致命结果（非幸存者）和临床结果阳性（幸存者）的患者的血样。RNA-Seq 显示，COVID-19 幸存者和非幸存者在入住 ICU 时全血中 93 个基因的转录水平存在显着差异。这些差异在第 7 天变得更加明显，产生了 290 个差异表达基因。许多已鉴定的基因在造血细胞的分化中发挥作用。为了进行验证，我们设计了一种针对 C 型凝集素结构域家族 12 成员 A ( CLEC12A ) 和乙酰胆碱酯酶 ( ACHE), 两个转录本在两个时间点都显示出区分幸存者和非幸存者的最高潜力。使用我们的联合 RT-qPCR 分析，我们检查了 33 个样本，以准确预测患者在 ICU 入院时的存活率，AUROC 曲线为 0.931 (95% CI = 0.814–1.000)。与包括 CRP 和 PCT 组合（AUROC = 0.403，95% CI = 0.108-0.697）或 SOFA 评分（AUROC = 0.701 95% CI = 0.451-0.951）在内的标准临床生物标志物相比， CLEC12A和ACHE显示出更好的患者预后预测。 0. 因此，分析血液中的CLEC12A和ACHE基因表达可能为重症 COVID-19 患者的早期风险分层提供一种有前途的方法。