Serum Proteomics in COVID-19 Patients: Altered Coagulation and Complement Status as a Function of IL-6 Level
Serum Proteomics in COVID-19 Patients: Altered Coagulation and Complement Status as a Function of IL-6 Level
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DOI：
10.1021/acs.jproteome.0c00365
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发表时间：
2020-11-06
影响因子：
4.4
通讯作者：
Hansen, Kirk C.
中科院分区：
文献类型：
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作者：
D'Alessandro, Angelo;Thomas, Tiffany;Hansen, Kirk C.
截至2020年5月29日，全球已有超过500万人的β冠状病毒SARS-CoV-2检测呈阳性，其中三分之一仅在美国。这些感染与一种称为COVID-19的疾病的发展有关，该疾病的特征是几种症状，包括持续性干咳、呼吸急促、寒战、肌肉疼痛、头痛、味觉或嗅觉丧失以及胃肠道不适。COVID-19的特点是死亡率升高（仅在美国就有超过10万人死亡），主要是由于血栓炎性并发症，在最严重的情况下会损害肺灌注和全身氧合。虽然促炎细胞因子（如白介素-6（IL-6））的水平与疾病的严重程度相关，但关于IL-6水平对COVID-19患者蛋白质组的影响知之甚少。本研究首次对COVID-19患者的血清进行了蛋白质组学分析，根据IL-6的循环水平进行分层，并与炎症和肾功能标志物相关。作为IL-6水平的函数，我们确定了各种凝血因子的血清水平的显著失调，伴随着抗纤维蛋白溶解组分水平的增加，包括几种丝氨酸蛋白酶抑制剂（SERPIN）。伴随补体级联和抗菌酶的上调，尤其是在IL-6水平最高的受试者中，这与这些受试者的急性期应答加重一致。尽管我们的结果是观察性的，但它们突出了严重COVID-19疾病中纤溶级联反应抑制组分水平的明显增加，为COVID-19凝血病并发症的病因学提供了潜在线索，并为潜在的治疗干预措施铺平了道路，例如使用促纤溶药物。本研究的原始数据可通过ProteomeXchange获得，标识符为PXD 020601。
Over 5 million people around the world have tested positive for the beta coronavirus SARS-CoV-2 as of May 29, 2020, a third of which are in the United States alone. These infections are associated with the development of a disease known as COVID-19, which is characterized by several symptoms, including persistent dry cough, shortness of breath, chills, muscle pain, headache, loss of taste or smell, and gastrointestinal distress. COVID-19 has been characterized by elevated mortality (over 100 thousand people have already died in the US alone), mostly due to thromboinflammatory complications that impair lung perfusion and systemic oxygenation in the most severe cases. While the levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) have been associated with the severity of the disease, little is known about the impact of IL-6 levels on the proteome of COVID-19 patients. The present study provides the first proteomics analysis of sera from COVID-19 patients, stratified by circulating levels of IL-6, and correlated to markers of inflammation and renal function. As a function of IL-6 levels, we identified significant dysregulation in serum levels of various coagulation factors, accompanied by increased levels of antifibrinolytic components, including several serine protease inhibitors (SERPINs). These were accompanied by up-regulation of the complement cascade and antimicrobial enzymes, especially in subjects with the highest levels of IL-6, which is consistent with an exacerbation of the acute phase response in these subjects. Although our results are observational, they highlight a clear increase in the levels of inhibitory components of the fibrinolytic cascade in severe COVID-19 disease, providing potential clues related to the etiology of coagulopathic complications in COVID-19 and paving the way for potential therapeutic interventions, such as the use of pro-fibrinolytic agents. Raw data for this study are available through ProteomeXchange with identifier PXD020601.