Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.

患有冠状病毒病19（COVID-19）的患者发生血栓性动脉和静脉阻塞的风险很高。但是，在某些患者中也观察到出血并发症。了解凝血和纤维蛋白溶解之间的平衡将有助于为预防血栓形成和纤维蛋白靶向疗法的潜在实用性提供最佳方法。该研究包括118名住院的COVID-19患者和30名健康对照。我们测量了组织型纤溶酶原激活物（tPA）和纤溶酶原激活物抑制剂1（PAI-1）的血浆抗原水平，并进行了自发的血块溶解测定。我们发现住院COVID-19的患者的tPA和PAI-1水平明显升高。这两个因素均显示与嗜中性粒细胞计数和嗜中性粒细胞活化标志物密切相关。高水平的tPA和PAI-1与呼吸状况恶化有关。特别是高水平的tPA，与死亡率和自发离体血凝块溶解的显着增强密切相关。尽管在COVID-19患者中tPA和PAI-1均升高，但tPA的极高水平会增强自发性纤维蛋白溶解，并且在某些患者中与死亡率显着相关。这些数据表明，COVID-19中的纤维蛋白溶解稳态是复杂的，一部分患者表达了可能有利于纤维蛋白溶解的因子平衡。必须进一步研究tPA作为生物标志物。极高水平的tPA会增强自发性纤维蛋白溶解，并且在某些患者中与死亡率显着相关。这些数据表明，COVID-19中的纤维蛋白溶解稳态是复杂的，一部分患者表达了可能有利于纤维蛋白溶解的因子平衡。必须进一步研究tPA作为生物标志物。极高水平的tPA会增强自发性纤维蛋白溶解，并且在某些患者中与死亡率显着相关。这些数据表明，COVID-19中的纤维蛋白溶解稳态是复杂的，一部分患者表达了可能有利于纤维蛋白溶解的因子平衡。必须进一步研究tPA作为生物标志物。