Mester Patricia, Amend Pablo, Schmid Stephan, Wenzel Jürgen J, Höring Marcus, Liebisch Gerhard, Krautbauer Sabrina, Müller Martina, Buechler Christa, Pavel Vlad
Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany.
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.
Infect Dis Rep. 2024 Jul 17;16(4):593-607. doi: 10.3390/idr16040045.
SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9 regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC) were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival. The current study suggests that the imbalance between CE and FC levels is associated with disease severity and mortality in patients with COVID-19.
研究表明，在脓毒症中，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染会诱导血浆中前蛋白转化酶枯草溶菌素/克新蛋白酶9型（PCSK9）水平升高。在此，我们研究血清PCSK9水平与疾病严重程度之间的关联。对55名对照者、40名中度新冠肺炎患者和60名重度新冠肺炎患者的血清进行了PCSK9检测。与对照组相比，中度新冠肺炎患者的血清PCSK9水平升高，重度病例中进一步升高。在重度新冠肺炎患者中，PCSK9水平与C反应蛋白、细菌二重感染、干预措施或生存率无关。PCSK9调节循环胆固醇水平，使用高分辨率混合四极杆-轨道阱质谱仪通过直接流动注射分析对15种胆固醇酯（CE）和游离胆固醇（FC）进行了定量。与中度新冠肺炎相比，重度新冠肺炎中大多数脂肪酸链较短的CE种类减少，在重度新冠肺炎患者中，没有CE种类与PCSK9相关。在重度新冠肺炎患者中，所有CE种类的水平均与C反应蛋白呈负相关。值得注意的是，与中度新冠肺炎相比，重度新冠肺炎中FC升高。FC/CE比值与炎症标志物呈正相关，且与死亡相关。当前研究表明，CE和FC水平之间的失衡与新冠肺炎患者的疾病严重程度和死亡率相关。
