新型冠状病毒肺炎的肺血管内皮细胞炎症、血栓形成和血管生成。
Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19.
机构信息
From the Institute of Pathology and Department of Molecular Pathology, Helios University Clinic Wuppertal, University of Witten-Herdecke, Wuppertal (M.A.), the Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz (M.A.), the Institute of Pathology (M.K., F.L., C.W., H.S., D.J.), the Department of Cardiothoracic, Transplantation, and Vascular Surgery (A.H.), and the Clinic of Pneumology (T.W.), Hannover Medical School, and the German Center for Lung Research, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) (M.K., A.H., T.W., F.L., C.W., H.S., D.J.), Hannover - all in Germany; the Laboratory of Respiratory Diseases, BREATH, Department of Chronic Diseases, Metabolism, and Aging, KU Leuven, Leuven, Belgium (S.E.V., A.V.); the Institute of Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland (A.T.); and the Angiogenesis Foundation, Cambridge (W.W.L., V.W.L.), and the Laboratory of Adaptive and Regenerative Biology and the Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston (S.J.M.) - all in Massachusetts.
出版信息
N Engl J Med. 2020 Jul 9;383(2):120-128. doi: 10.1056/NEJMoa2015432. Epub 2020 May 21.
BACKGROUND
Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.
METHODS
We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression.
RESULTS
In patients who died from Covid-19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth - predominantly through a mechanism of intussusceptive angiogenesis - was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).
CONCLUSIONS
In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.).
背景
进行性呼吸衰竭是导致 2019 年冠状病毒病（COVID-19）大流行患者死亡的主要原因。尽管人们对该疾病的病理生理学广泛感兴趣，但对于 COVID-19 死亡患者外周肺相关的形态和分子变化，人们了解甚少。
方法
我们检查了 COVID-19 死亡患者尸检时获得的 7 个肺组织，并与流感 A(H1N1)感染导致的急性呼吸窘迫综合征（ARDS）死亡患者尸检时获得的 7 个肺组织和 10 个年龄匹配的未感染对照肺组织进行了比较。使用 7 色免疫组织化学分析、微计算机断层扫描成像、扫描电子显微镜、腐蚀铸造和直接多重基因表达测量来研究这些肺组织。
结果
在 COVID-19 相关或流感相关呼吸衰竭死亡的患者中，外周肺的组织学模式为弥漫性肺泡损伤，伴有血管周围 T 细胞浸润。COVID-19 患者的肺还表现出独特的血管特征，包括严重的内皮损伤，伴有细胞内病毒和细胞膜破裂。COVID-19 患者的肺血管组织学分析显示广泛的微血栓形成伴微血管病。COVID-19 患者的肺泡毛细血管微血栓比流感患者多 9 倍（P<0.001）。在 COVID-19 患者的肺中，新血管生长的数量-主要通过内陷性血管生成的机制-比流感患者高 2.7 倍（P<0.001）。
结论
在我们的小系列中，血管生成将 COVID-19 的肺部病理生理学与同样严重的流感病毒感染区分开来。我们观察到的普遍性和临床意义需要进一步研究来确定。（由美国国立卫生研究院等资助）。
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