Carnevale Roberto, Nocella Cristina, Marocco Raffaella, Zuccalà Paola, Carraro Anna, Picchio Vittorio, Oliva Alessandra, Cangemi Roberto, Miele Maria Claudia, De Angelis Massimiliano, Cancelli Francesca, Casciaro Giovanni Enrico, Cristiano Luca, Pignatelli Pasquale, Frati Giacomo, Venditti Mario, Pugliese Francesco, Mastroianni Claudio Maria, Violi Francesco, Ridola Lorenzo, Del Borgo Cosmo, Palmerio Silvia, Valenzi Emiliano, Carnevale Rita, Alvaro Domenico, Lichtner Miriam, Cardinale Vincenzo
Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
IRCCS Neuromed, 86077 Pozzilli, Italy.
Antioxidants (Basel). 2024 Oct 17;13(10):1260. doi: 10.3390/antiox13101260.
Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favor thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of this study was to analyze the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer, and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin, and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer, and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with ARDS compared with those without ARDS and inversely associated with LPS. In the COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp and LPS and D-dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation, and low serum albumin may account for low-grade endotoxemia and may be implicated in thrombotic events in COVID-19.
在新冠肺炎患者中已检测到脂多糖（LPS）引起的低度内毒素血症，其可通过引发促炎和促凝状态而促进血栓形成。本研究的目的是分析新冠肺炎低度内毒素血症的机制及其与氧化应激和凝血激活血栓形成的关系。我们检测了175例新冠肺炎患者（分为有或无急性呼吸窘迫综合征（ARDS））和50名健康受试者的血清sNOX2-dp、闭合蛋白、LPS、D-二聚体和白蛋白水平。与对照组相比，新冠肺炎患者的sNOX2-dp、LPS、闭合蛋白、D-二聚体、白蛋白和hs-CRP基线水平显著更高。在患有ARDS的新冠肺炎患者中，与没有ARDS的新冠肺炎患者相比，sNOX2-dp、LPS、闭合蛋白、D-二聚体和hs-CRP显著更高。相反，ARDS患者的白蛋白浓度低于没有ARDS的患者，且与LPS呈负相关。在新冠肺炎队列中，根据sNOX2-dp和LPS四分位数，ARDS患者的数量逐渐增加；在新冠肺炎患者中检测到LPS与sNOX2-dp以及LPS与D-二聚体之间存在显著相关性。在多变量逻辑回归模型中，LPS/白蛋白水平和D-二聚体可预测血栓形成事件。在新冠肺炎患者中，LPS与高凝状态和疾病严重程度显著相关。在体外，LPS可增加内皮氧化应激和凝血生物标志物，而白蛋白治疗可降低这些指标。总之，肠道屏障通透性受损、NOX2激活增加和血清白蛋白水平降低可能是新冠肺炎低度内毒素血症的原因，并可能与血栓形成事件有关。
