A deeper understanding of COVID-19 on human molecular pathophysiology is urgently needed as a foundation for the discovery of new biomarkers and therapeutic targets. Here we applied mass spectrometry (MS)-based proteomics to measure serum proteomes of COVID-19 patients and symptomatic, but PCR-negative controls, in a time-resolved manner. In 262 controls and 458 longitudinal samples of 31 patients, hospitalized for COVID-19, a remarkable 26% of proteins changed significantly. Bioinformatics analyses revealed co-regulated groups and shared biological functions. Proteins of the innate immune system such as CRP, SAA1, CD14, LBP, and LGALS3BP decreased early in the time course. Regulators of coagulation (APOH, FN1, HRG, KNG1, PLG) and lipid homeostasis (APOA1, APOC1, APOC2, APOC3, PON1) increased over the course of the disease. A global correlation map provides a system-wide functional association between proteins, biological processes, and clinical chemistry parameters. Importantly, five SARS-CoV-2 immunoassays against antibodies revealed excellent correlations with an extensive range of immunoglobulin regions, which were quantified by MS-based proteomics. The high-resolution profile of all immunoglobulin regions showed individual-specific differences and commonalities of potential pathophysiological relevance.

中文翻译：

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COVID-19 中的高分辨率血清蛋白质组轨迹揭示了患者特异性血清转化

迫切需要更深入地了解 COVID-19 对人类分子病理生理学的影响，作为发现新生物标志物和治疗靶点的基础。在这里，我们应用基于质谱 (MS) 的蛋白质组学以时间分辨的方式测量 COVID-19 患者和有症状但 PCR 阴性对照的血清蛋白质组。在 262 名对照者和 31 名因 COVID-19 住院患者的 458 份纵向样本中，高达 26% 的蛋白质发生了显着变化。生物信息学分析揭示了共同调控的群体和共享的生物学功能。先天免疫系统的蛋白质，如 CRP、SAA1、CD14、LBP 和 LGALS3BP 在早期就减少了。凝血调节因子（APOH、FN1、HRG、KNG1、PLG）和脂质稳态调节因子（APOA1、APOC1、APOC2、APOC3、PON1）随着疾病进程而增加。全局相关图提供了蛋白质、生物过程和临床化学参数之间的全系统功能关联。重要的是，针对抗体的五种 SARS-CoV-2 免疫测定显示与广泛的免疫球蛋白区域具有良好的相关性，这些区域通过基于 MS 的蛋白质组学进行了量化。所有免疫球蛋白区域的高分辨率图谱显示了个体特异性差异和潜在病理生理学相关性的共性。