PDF(Pubmed)
Abstract：
Although the COVID-19 pandemic has ended, it is important to understand the pathology of severe SARS-CoV-2 infection associated with respiratory failure and high mortality. The plasma proteome, including protein modification by lipid peroxidation products in COVID-19 survivors (COVID-19; n = 10) and deceased individuals (CovDeath; n = 10) was compared in samples collected upon admission to the hospital, when there was no difference in their status, with that of healthy individuals (Ctr; n = 10). The obtained results show that COVID-19 development strongly alters the expression of proteins involved in the regulation of exocytosis and platelet degranulation (top 20 altered proteins indicated by analysis of variance; p-value (False Discovery Rate) cutoff at 5%). These changes were most pronounced in the CovDeath group. In addition, the levels of 4-hydroxynonenal (4-HNE) adducts increased 2- and 3-fold, whereas malondialdehyde (MDA) adducts increased 7- and 2.5-fold, respectively, in COVID-19 and CovDeath groups. Kinases and proinflammatory proteins were particularly affected by these modifications. Protein adducts with 15-deoxy-12,14-prostaglandin J2 (15d-PGJ2) were increased 2.5-fold in COVID-19 patients, including modifications of proteins such as p53 and STAT3, whereas CovDeath showed a decrease of approximately 60% compared with Ctr. This study for the first time demonstrates the formation of lipid metabolism products-protein adducts in plasma from survived and deceased COVID-19 patients, significantly distinguishing them, which may be a predictor of the course of SARS-CoV-2 infection.
摘要：
尽管COVID-19大流行已经结束，了解严重SARS-CoV-2感染与呼吸衰竭和高死亡率相关的病理学非常重要。血浆蛋白质组，在入院时收集的样本中，比较了COVID-19幸存者（COVID-19；n=10）和死者（CovDeath；n=10）的脂质过氧化产物对蛋白质的修饰，当他们的地位没有区别时，与健康个体(Ctr；n=10)。获得的结果表明，COVID-19的发展强烈改变了参与胞吐和血小板脱粒调节的蛋白质的表达（方差分析显示前20种改变的蛋白质；p值（错误发现率）截止为5％）。这些变化在CovDeath组中最为明显。此外,4-羟基壬烯醛（4-HNE）加合物的水平增加了2倍和3倍，而丙二醛（MDA）加合物增加了7倍和2.5倍，分别,在COVID-19和CovDeath组中。激酶和促炎蛋白尤其受到这些修饰的影响。在COVID-19患者中，与15-脱氧-12,14-前列腺素J2（15d-PGJ2）的蛋白质加合物增加了2.5倍，包括p53和STAT3等蛋白质的修饰，而CovDeath与Ctr相比降低了约60％。这项研究首次证明了存活和死亡的COVID-19患者血浆中脂质代谢产物-蛋白质加合物的形成，显著区分它们，这可能是SARS-CoV-2感染过程的预测因素。
