在一组患有不同严重程度的COVID-19疾病的患者中进行了详细的蛋白质组学分析,发现补体和凝血级联反应中的生物标志物是疾病严重程度的生物标志物;然而,目前尚不清楚这些蛋白质是否与其他条件有足够的差异而被视为生物标志物.
有前景的,T2D(n=23)和对照(n=23)的平行研究。进行高胰岛素钳夹,并在T2D[4.5±0.07mmol/L(81±1.2mg/dl)]中诱导正常血糖1小时,随后血糖降至≤2.0mmol/L(36mg/dl)。使用慢解离速率修饰适体(SOMA)扫描测量补体和凝血级联的蛋白质组学分析。
测量了34种蛋白质。在基线,发现18个中的4个在T2D与对照的血小板脱颗粒方面存在差异[中性粒细胞激活肽-2(p=0.014),血小板反应蛋白-1(p=0.012),血小板因子-4(p=0.007),和激素原-1(p=0.05)],而16种蛋白质中有3种在补体和凝血级联反应方面存在差异[凝血因子IX(p<0.05),激素原-1(p=0.05),和肝素辅因子-2(p=0.007)];STRING分析证明了这些蛋白质彼此之间的密切关系。与基线相比,T2D中诱导的血糖正常没有蛋白质变化。在低血糖时,然而,对照中的四种蛋白质从基线变化[血小板反应蛋白-1(p<0.014),血小板因子-4(p<0.01),血小板碱性蛋白(p<0.008),和维生素K依赖性蛋白C(p<0.00003)],一种蛋白质在T2D中改变[维生素K依赖性蛋白质C,(p<0.0002)]。
T2D与对照组相比,34种蛋白质中的7种被认为是血小板脱颗粒和补体和凝血级联反应中COVID-19严重程度的生物标志物,随着低血糖发生进一步的变化,表明这些生物标志物的验证是至关重要的。目前尚不清楚T2D中的这些蛋白质变化是否可以预测这些患者的COVID-19疾病恶化。
https://clinicaltrials.gov/,标识符NCT03102801。
Detailed proteomic analysis in a cohort of patients with differing severity of COVID-19 disease identified biomarkers within the complement and coagulation cascades as biomarkers for disease severity has been reported; however, it is unclear if these proteins differ sufficiently from other conditions to be considered as biomarkers.
A prospective, parallel study in T2D (n = 23) and controls (n = 23). A hyperinsulinemic clamp was performed and normoglycemia induced in T2D [4.5 ± 0.07 mmol/L (81 ± 1.2 mg/dl)] for 1-h, following which blood glucose was decreased to ≤2.0 mmol/L (36 mg/dl). Proteomic analysis for the complement and coagulation cascades were measured using Slow Off-rate Modified Aptamer (SOMA)-scan.
Thirty-four proteins were measured. At baseline, 4 of 18 were found to differ in T2D versus controls for platelet degranulation [Neutrophil-activating peptide-2 (p = 0.014), Thrombospondin-1 (p = 0.012), Platelet factor-4 (p = 0.007), and Kininogen-1 (p = 0.05)], whilst 3 of 16 proteins differed for complement and coagulation cascades [Coagulation factor IX (p < 0.05), Kininogen-1 (p = 0.05), and Heparin cofactor-2 (p = 0.007)]; STRING analysis demonstrated the close relationship of these proteins to one another. Induced euglycemia in T2D showed no protein changes versus baseline. At hypoglycemia, however, four proteins changed in controls from baseline [Thrombospondin-1 (p < 0.014), platelet factor-4 (p < 0.01), Platelet basic protein (p < 0.008), and Vitamin K-dependent protein-C (p < 0.00003)], and one protein changed in T2D [Vitamin K-dependent protein-C, (p < 0.0002)].
Seven of 34 proteins suggested to be biomarkers of COVID-19 severity within the platelet degranulation and complement and coagulation cascades differed in T2D versus controls, with further changes occurring at hypoglycemia, suggesting that validation of these biomarkers is critical. It is unclear if these protein changes in T2D may predict worse COVID-19 disease for these patients.
https://clinicaltrials.gov/, identifier NCT03102801.