Microvascular dysfunction in COVID-19: the MYSTIC study.
Microvascular dysfunction in COVID-19: the MYSTIC study.
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COVID-19微血管功能障碍：MYSTIC研究
DOI：
10.1007/s10456-020-09753-7
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发表时间：
2021-03
期刊：
影响因子：
9.8
通讯作者：
Kümpers P
中科院分区：
文献类型：
--
作者：
Rovas A;Osiaevi I;Buscher K;Sackarnd J;Tepasse PR;Fobker M;Kühn J;Braune S;Göbel U;Thölking G;Gröschel A;Pavenstädt H;Vink H;Kümpers P
临床前和尸检研究支持了这样一种假设，即血管内皮失调可能在COVID-19的ARDS和多器官衰竭的发病机制中发挥核心作用。全面表征和量化COVID-19患者的微血管改变。 在这项前瞻性、观察性、横断面、多中心研究中，非连续入组了中重度或危重型COVID-19住院成人患者（n = 23）。15名健康志愿者作为对照。所有参与者均通过侧流暗场成像进行活体显微镜检查，以量化舌下微血管中的血管密度、红细胞速度（VRBC）和糖萼尺寸（灌注边界区域，PBR）。循环水平的内皮细胞和糖萼相关标志物的多重邻近延伸试验和酶联免疫吸附试验进行了测量。COVID-19患者显示血管密度降低高达90%，几乎仅限于小毛细血管（直径4-6 µm），VRBC也显著降低。特别是，机械通气患者显示出严重的糖萼损伤，如较高的PBR值所示（即，更薄的糖萼）和增加脱落的糖萼成分的血液水平。在COVID-19中，几种内皮功能障碍的标志物增加，并与疾病严重程度相关。PBR（AUC 0.75，p = 0.01）、ADAMTS 13（血管性血友病因子裂解蛋白酶; AUC 0.74，p = 0.02）和血管内皮生长因子A（VEGF-A; AUC 0.73，p = 0.04）显示出预测60天住院死亡率的最佳区分能力。我们的数据清楚地显示了COVID-19患者微循环和内皮糖萼的严重改变。未来的治疗方法应考虑COVID-19全身血管受累的重要性。本文的在线版本（10.1007/s10456-020-09753-7）包含补充材料，可供授权用户使用。
Pre-clinical and autopsy studies have fueled the hypothesis that a dysregulated vascular endothelium might play a central role in the pathogenesis of ARDS and multi-organ failure in COVID-19. To comprehensively characterize and quantify microvascular alterations in patients with COVID-19. Hospitalized adult patients with moderate-to-severe or critical COVID-19 (n = 23) were enrolled non-consecutively in this prospective, observational, cross-sectional, multi-center study. Fifteen healthy volunteers served as controls. All participants underwent intravital microscopy by sidestream dark field imaging to quantify vascular density, red blood cell velocity (VRBC), and glycocalyx dimensions (perfused boundary region, PBR) in sublingual microvessels. Circulating levels of endothelial and glycocalyx-associated markers were measured by multiplex proximity extension assay and enzyme-linked immunosorbent assay. COVID-19 patients showed an up to 90% reduction in vascular density, almost exclusively limited to small capillaries (diameter 4–6 µm), and also significant reductions of VRBC. Especially, patients on mechanical ventilation showed severe glycocalyx damage as indicated by higher PBR values (i.e., thinner glycocalyx) and increased blood levels of shed glycocalyx constituents. Several markers of endothelial dysfunction were increased and correlated with disease severity in COVID-19. PBR (AUC 0.75, p = 0.01), ADAMTS13 (von Willebrand factor-cleaving protease; AUC 0.74, p = 0.02), and vascular endothelial growth factor A (VEGF-A; AUC 0.73, p = 0.04) showed the best discriminatory ability to predict 60-day in-hospital mortality. Our data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19. Future therapeutic approaches should consider the importance of systemic vascular involvement in COVID-19. The online version of this article (10.1007/s10456-020-09753-7) contains supplementary material, which is available to authorized users.
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DOI：
10.1186/s13049-018-0483-4
发表时间：
2018-02-14
期刊：
Scandinavian journal of trauma, resuscitation and emergency medicine
影响因子：
--
作者：
Rovas A;Lukasz AH;Vink H;Urban M;Sackarnd J;Pavenstädt H;Kümpers P
通讯作者：
Kümpers P
影响因子：
4.3
作者：
Sack KD;Kellum JA;Parikh SM
通讯作者：
Parikh SM
影响因子：
15.8
作者：
Parikh SM;Mammoto T;Schultz A;Yuan HT;Christiani D;Karumanchi SA;Sukhatme VP
通讯作者：
Sukhatme VP
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
82.9
作者：
Schmidt, Eric P.;Yang, Yimu;Janssen, William J.;Gandjeva, Aneta;Perez, Mario J.;Barthel, Lea;Zemans, Rachel L.;Bowman, Joel C.;Koyanagi, Dan E.;Yunt, Zulma X.;Smith, Lynelle P.;Cheng, Sara S.;Overdier, Katherine H.;Thompson, Kathy R.;Geraci, Mark W.;Douglas, Ivor S.;Pearse, David B.;Tuder, Rubin M.
通讯作者：
Tuder, Rubin M.