The Outcome of Critically Ill COVID-19 Patients Is Linked to Thromboinflammation Dominated by the Kallikrein/Kinin System.
The Outcome of Critically Ill COVID-19 Patients Is Linked to Thromboinflammation Dominated by the Kallikrein/Kinin System.
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重症COVID-19患者的结局与由激肽释放酶/激肽系统主导的血栓性炎症有关。
DOI：
10.3389/fimmu.2021.627579
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发表时间：
2021
影响因子：
7.3
通讯作者：
Nilsson B
中科院分区：
文献类型：
--
作者：
Lipcsey M;Persson B;Eriksson O;Blom AM;Fromell K;Hultström M;Huber-Lang M;Ekdahl KN;Frithiof R;Nilsson B
严重COVID-19的一个重要表现是与血管内皮细胞增生、血栓形成和血管生成相关的ARDS样肺损伤。血管内先天免疫系统（IIIS），包括补体、接触、凝血和纤溶系统，对识别和清除体内微生物和碎片至关重要，可能参与COVID-19 ARDS的发病机制。在一项前瞻性研究中，在乌普萨拉大学医院ICU收治的前66名COVID-19患者中研究了IIIS激活的生物标志物，在第1天进行了横断面研究，并在19名患者中进行了长达一个月的纵向研究。将IIIS分析与生化参数、临床结局和生存率进行比较。血液级联系统激活导致过度反应性结膜血栓炎症，反映在个体级联系统组分的消耗中，例如，FXII、前激肽释放酶和高分子量激肽原，以及活化产物水平增加，C4d、C3 a、C3 d、g、sC 5 b-9、达特和D-二聚体。血液级联系统与器官损伤、疾病严重程度评分和生存率之间存在强相关性。我们发现，重症COVID-19患者显示出与肺、心脏、肾脏等器官损伤和死亡相关的IIIS联合激活。我们提出的证据表明，补体，特别是激肽释放酶/激肽系统被强烈激活，这两个系统的预后标志物的患者的结果表明他们的作用，在驱动炎症。已经获得许可的激肽释放酶/激肽抑制剂是治疗COVID-19重症患者的潜在药物。
An important manifestation of severe COVID-19 is the ARDS-like lung injury that is associated with vascular endothelialitis, thrombosis, and angiogenesis. The intravascular innate immune system (IIIS), including the complement, contact, coagulation, and fibrinolysis systems, which is crucial for recognizing and eliminating microorganisms and debris in the body, is likely to be involved in the pathogenesis of COVID-19 ARDS. Biomarkers for IIIS activation were studied in the first 66 patients with COVID-19 admitted to the ICU in Uppsala University Hospital, both cross-sectionally on day 1 and in 19 patients longitudinally for up to a month, in a prospective study. IIIS analyses were compared with biochemical parameters and clinical outcome and survival. Blood cascade systems activation leading to an overreactive conjunct thromboinflammation was demonstrated, reflected in consumption of individual cascade system components, e.g., FXII, prekallikrein, and high molecular weight kininogen and in increased levels of activation products, e.g., C4d, C3a, C3d,g, sC5b-9, TAT, and D-dimer. Strong associations were found between the blood cascade systems and organ damage, illness severity scores, and survival. We show that critically ill COVID-19 patients display a conjunct activation of the IIIS that is linked to organ damage of the lung, heart, kidneys, and death. We present evidence that the complement and in particular the kallikrein/kinin system is strongly activated and that both systems are prognostic markers of the outcome of the patients suggesting their role in driving the inflammation. Already licensed kallikrein/kinin inhibitors are potential drugs for treatment of critically ill patients with COVID-19.
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影响因子：
3.7
作者：
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通讯作者：
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