The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in two independent cohorts of critically ill COVID-19 patients in comparison to patients suffering from severe acute respiratory distress syndrome due to influenza virus (ARDS-influenza). Compatible with this data, we report rapid consumption of FXII in COVID-19, but not in ARDS-influenza, plasma. Interestingly, the kaolin clotting time was not prolonged in COVID-19 as compared to ARDS-influenza. Using confocal and electron microscopy, we show that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggers formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, we observed clot lysis in 30% of COVID-19 patients and 84% of ARDS-influenza subjects. Analysis of lung tissue sections revealed wide-spread extra- and intra-vascular compact fibrin deposits in COVID-19. Together, our results indicate that elevated fibrinogen levels and increased FXII activation rate promote thrombosis and thrombolysis resistance via enhanced thrombus formation and stability in COVID-19.

中文翻译：

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改变的纤维蛋白凝块结构导致严重 COVID-19 的血栓形成风险

血栓事件的高发生率表明接触系​​统通路在 COVID-19 病理学中可能发挥作用。在这里，我们证明了与因流感病毒（ARDS-influenza）而患严重急性呼吸窘迫综合征的患者相比，两个独立的重症 COVID-19 患者队列中因子 XII（FXII）及其激活产物的水平发生了变化。与此数据兼容，我们报告了 COVID-19 中 FXII 的快速消耗，但在 ARDS 流感、血浆中则不然。有趣的是，与 ARDS 流感相比，COVID-19 的高岭土凝血时间没有延长。使用共聚焦和电子显微镜，我们发现 FXII 激活率的增加，连同纤维蛋白原水平的升高，触发了 COVID-19 中抗纤维蛋白溶解、具有细纤维和小孔的致密凝块的形成。因此，我们在 30% 的 COVID-19 患者和 84% 的 ARDS 流感患者中观察到了血块溶解。肺组织切片分析显示 COVID-19 中广泛存在血管内外致密纤维蛋白沉积。总之，我们的结果表明纤维蛋白原水平升高和 FXII 活化率增加促进血栓形成和溶栓抵抗通过增强 COVID-19 中的血栓形成和稳定性。