Mannose-Binding Lectin is Associated with Thrombosis and Coagulopathy in Critically Ill COVID-19 Patients
Mannose-Binding Lectin is Associated with Thrombosis and Coagulopathy in Critically Ill COVID-19 Patients
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DOI：
10.1055/s-0040-1715835
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发表时间：
2020-09-01
影响因子：
6.7
通讯作者：
Frithiof, Robert
中科院分区：
文献类型：
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作者：
Eriksson, Oskar;Hultstrom, Michael;Frithiof, Robert
持续的COVID-19疫情在全球范围内造成了巨大的发病率和死亡率，并对社会产生了深远的影响。COVID-19患者发生血栓栓塞（TE）并发症的风险增加，尽管进行了药物血栓预防，但仍会发生血栓栓塞并发症。COVID-19相关凝血病背后的机制仍不清楚。甘露糖结合凝集素（MBL）是一种模式识别分子，启动补体激活的凝集素途径，已被认为是血栓炎症过程中血液凝固的潜在放大剂。在这里，我们描述了来自一组在三级医院中心重症监护室（ICU）接受治疗的重症COVID-19患者（n =65）的数据。一部分患者的MBL血浆水平和ICU入院时的活动度显著升高，出现症状性TE的患者（14%）的MBL水平显著高于无TE的患者。MBL与血浆D-二聚体水平（COVID-19凝血障碍的标志物）密切相关，但与炎症程度或其他器官功能障碍无关。总之，我们已经确定通过MBL途径的补体激活是一种新的扩增机制，有助于重症COVID-19患者的病理性血栓形成。MBL通路的药理学靶向可能是COVID-19血栓形成的一种新的治疗选择。MBL水平的实验室检测可能对识别处于TE事件风险中的COVID-19患者具有价值。
The ongoing COVID-19 pandemic has caused significant morbidity and mortality worldwide, as well as profound effects on society. COVID-19 patients have an increased risk of thromboembolic (TE) complications, which develop despite pharmacological thromboprophylaxis. The mechanism behind COVID-19-associated coagulopathy remains unclear. Mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, has been suggested as a potential amplifier of blood coagulation during thromboinflammation. Here we describe data from a cohort of critically ill COVID-19 patients ( n =65) treated at a tertiary hospital center intensive care unit (ICU). A subset of patients had strongly elevated MBL plasma levels, and activity upon ICU admission, and patients who developed symptomatic TE (14%) had significantly higher MBL levels than patients without TE. MBL was strongly correlated to plasma D-dimer levels, a marker of COVID-19 coagulopathy, but showed no relationship to degree of inflammation or other organ dysfunction. In conclusion, we have identified complement activation through the MBL pathway as a novel amplification mechanism that contributes to pathological thrombosis in critically ill COVID-19 patients. Pharmacological targeting of the MBL pathway could be a novel treatment option for thrombosis in COVID-19. Laboratory testing of MBL levels could be of value for identifying COVID-19 patients at risk for TE events.