Here, we recorded serum proteome profiles of 33 severe COVID-19 patients admitted to respiratory and intensive care units because of respiratory failure. We received, for most patients, blood samples just after admission and at two more later time points. With the aim to predict treatment outcome, we focused on serum proteins different in abundance between the group of survivors and non-survivors. We observed that a small panel of about a dozen proteins were significantly different in abundance between these two groups. The four structurally and functionally related type-3 cystatins AHSG, FETUB, histidine-rich glycoprotein, and KNG1 were all more abundant in the survivors. The family of inter-α-trypsin inhibitors, ITIH1, ITIH2, ITIH3, and ITIH4, were all found to be differentially abundant in between survivors and non-survivors, whereby ITIH1 and ITIH2 were more abundant in the survivor group and ITIH3 and ITIH4 more abundant in the non-survivors. ITIH1/ITIH2 and ITIH3/ITIH4 also showed opposite trends in protein abundance during disease progression. We defined an optimal panel of nine proteins for mortality risk assessment. The prediction power of this mortality risk panel was evaluated against two recent COVID-19 serum proteomics studies on independent cohorts measured in other laboratories in different countries and observed to perform very well in predicting mortality also in these cohorts. This panel may not be unique for COVID-19 as some of the proteins in the panel have previously been annotated as mortality markers in aging and in other diseases caused by different pathogens, including bacteria.

中文翻译：

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预测重症 COVID-19 患者死亡率的血清蛋白质组特征。

在这里，我们记录了 33 名因呼吸衰竭入住呼吸和重症监护病房的重症 COVID-19 患者的血清蛋白质组谱。对于大多数患者，我们在入院后和之后的两个时间点接受了血液样本。为了预测治疗结果，我们专注于幸存者组和非幸存者组之间丰度不同的血清蛋白。我们观察到，这两组之间大约有十几种蛋白质在丰度方面存在显着差异。四种结构和功能相关的 3 型胱抑素 AHSG、FETUB、富含组氨酸的糖蛋白和 KNG1 在幸存者中都更丰富。α-胰蛋白酶抑制剂家族 ITIH1、ITIH2、ITIH3 和 ITIH4，都被发现在幸存者和非幸存者之间的含量不同，其中 ITIH1 和 ITIH2 在幸存者组中更丰富，而 ITIH3 和 ITIH4 在非幸存者组中更丰富。ITIH1/ITIH2 和 ITIH3/ITIH4 在疾病进展过程中也显示出相反的蛋白质丰度趋势。我们为死亡风险评估定义了一个由九种蛋白质组成的最佳面板。该死亡风险小组的预测能力根据最近在不同国家其他实验室测量的独立队列的两项 COVID-19 血清蛋白质组学研究进行了评估，并观察到在这些队列中也能很好地预测死亡率。该面板对于 COVID-19 可能不是唯一的，因为面板中的一些蛋白质之前已被注释为衰老和其他由不同病原体（包括细菌）引起的疾病的死亡率标志物。