Department of Pulmonary Medicine, Amsterdam UMC, Free University Amsterdam, Amsterdam, Netherlands.
Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC, Amsterdam, Netherlands.
Front Immunol. 2021 May 14;12:664209. doi: 10.3389/fimmu.2021.664209. eCollection 2021.
Systemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited.
To evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.
Paired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured.
In all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined.
Critically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory "storm" in severe COVID-19.
促凝和炎症机制的系统激活被认为与 COVID-19 的发病机制有关。关于 COVID-19 患者肺部中这些宿主反应途径的激活知之甚少。
评估持续存在急性呼吸窘迫综合征的危重症 COVID-19 患者中肺部局部和全身凝血及相互关联的炎症反应的激活情况。
从 17 例 COVID-19 相关持续存在急性呼吸窘迫综合征（机械通气>7 天）患者中获得机械通气开始后 1 周和 2 周时的配对支气管肺泡灌洗液和血浆样本，并与 8 例健康对照进行比较。将 34 种宿主反应生物标志物分为五个功能域（凝血、补体系统、细胞因子、趋化因子和生长因子）进行测量。
所有患者的所有功能域均被激活，尤其是在支气管肺泡隔中，D-二聚体、凝血酶-抗凝血酶复合物、可溶性组织因子、C1 抑制剂抗原和活性水平、组织型纤溶酶原激活物、纤溶酶原激活物抑制剂-1、可溶性 CD40 配体和可溶性 P 选择素（凝血）显著升高，此外，C3bc 和 C4bc（补体）和多种相互关联的细胞因子、趋化因子和生长因子也被激活。在开始机械通气后 3 至 4 周时获得随访样本的 10 例患者中，许多支气管肺泡和血浆宿主反应生物标志物水平下降。
危重症、机械通气的 COVID-19 患者在支气管肺泡隔中表现出强烈的与凝血、补体系统、细胞因子、趋化因子和生长因子相关的反应。这些结果表明，在严重 COVID-19 中存在局部肺部而非全身性的促凝和炎症“风暴”。
