Pine Alexander B, Meizlish Matthew L, Goshua George, Chang C-Hong, Zhang Hanming, Bishai Jason, Bahel Parveen, Patel Amisha, Gbyli Rana, Kwan Jennifer M, Won Christine H, Price Christina, Dela Cruz Charles S, Halene Stephanie, van Dijk David, Hwa John, Lee Alfred I, Chun Hyung J
Section of Hematology, Yale School of Medicine, New Haven, CT, USA.
Yale School of Medicine, New Haven, CT, USA.
Pulm Circ. 2020 Nov 25;10(4):2045894020966547. doi: 10.1177/2045894020966547. eCollection 2020 Oct-Dec.
Increase in thrombotic and microvascular complications is emerging to be a key feature of patients with critical illness associated with COVID-19 infection. While endotheliopathy is thought to be a key factor of COVID-19-associated coagulopathy, markers indicative of this process that are prognostic of disease severity have not been well-established in this patient population. Using plasma profiling of patients with COVID-19, we identified circulating markers that segregated with disease severity: markers of angiogenesis (VEGF-A, PDGF-AA and PDGF-AB/BB) were elevated in hospitalized patients with non-critical COVID-19 infection, while markers of endothelial injury (angiopoietin-2, FLT-3L, PAI-1) were elevated in patients with critical COVID-19 infection. In survival analysis, elevated markers of endothelial injury (angiopoietin-2, follistatin, PAI-1) were strongly predictive of in-hospital mortality. Our findings demonstrate that non-critical and critical phases of COVID-19 disease may be driven by distinct mechanisms involving key aspects of endothelial cell function, and identify drivers of COVID-19 pathogenesis and potential targets for future therapies.
血栓形成和微血管并发症的增加正逐渐成为与新型冠状病毒肺炎（COVID-19）感染相关的危重症患者的一个关键特征。虽然内皮病变被认为是COVID-19相关凝血病的一个关键因素，但在该患者群体中，指示这一过程且对疾病严重程度具有预后价值的标志物尚未得到充分确立。通过对COVID-19患者进行血浆分析，我们确定了与疾病严重程度相关的循环标志物：血管生成标志物（血管内皮生长因子-A、血小板衍生生长因子-AA和血小板衍生生长因子-AB/BB）在非重症COVID-19感染的住院患者中升高，而内皮损伤标志物（血管生成素-2、FMS样酪氨酸激酶3配体、纤溶酶原激活物抑制剂-1）在重症COVID-19感染患者中升高。在生存分析中，内皮损伤标志物（血管生成素-2、卵泡抑素、纤溶酶原激活物抑制剂-1）升高强烈预示着住院死亡率。我们的研究结果表明，COVID-19疾病的非重症和重症阶段可能由涉及内皮细胞功能关键方面的不同机制驱动，并确定了COVID-19发病机制的驱动因素以及未来治疗的潜在靶点。
