Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.
Mediclinic Stellenbosch, Stellenbosch, South Africa.
Semin Thromb Hemost. 2024 Mar;50(2):288-294. doi: 10.1055/s-0043-1769014. Epub 2023 May 19.
The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of von Willebrand factor (VWF), platelet factor 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), and platelet endothelial cell adhesion molecule (PECAM-1) in the soluble part of the blood. It was noteworthy that the mean level of α-2 antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We conclude that presence of microclotting, together with relatively high levels of six biomarkers known to be key drivers of endothelial and clotting pathology, points to thrombotic endothelialitis as a key pathological process in Long COVID.
目前，人们对长新冠持续症状的主流假说集中在免疫失调和自身抗体、广泛的器官损伤、病毒持续存在、纤维蛋白样微栓（捕获大量炎症分子）以及血小板过度激活上。在这里，我们发现在血液的可溶性部分，血管性血友病因子（von Willebrand factor，VWF）、血小板因子 4（platelet factor 4，PF4）、血清淀粉样蛋白 A（serum amyloid A，SAA）、α-2 抗纤溶酶（α-2 antiplasmin，α-2AP）、内皮白细胞黏附分子 1（endothelial-leukocyte adhesion molecule 1，E-selectin）和血小板内皮细胞黏附分子（platelet endothelial cell adhesion molecule，PECAM-1）的浓度显著升高。值得注意的是，长新冠患者α-2 抗纤溶酶的平均水平超过了实验室参考范围的上限，而与对照组相比，长新冠患者的其他 5 种标志物也显著升高。如果我们考虑到以前已经证明，这些炎症分子的很大一部分总负荷都被捕获在纤维蛋白溶解抵抗性的微栓内（从而降低了可溶性分子的表观水平），那么这是令人担忧的。我们的结论是，微栓形成的存在，加上六种已知是内皮和凝血病理关键驱动因素的生物标志物的相对高水平，表明血栓性血管炎是长新冠的一个关键病理过程。
