新冠病毒病可導致肺血管內皮炎、血栓形成和血管生成
作者：
小柯機器人發布時間：2020/5/24 23:48:32
研究人員檢查了通過屍檢從Covid-19死亡患者中獲得的7個肺臟，並將它們與死於甲型H1N1流感繼發的急性呼吸窘迫症候群（ARDS）患者的7個肺臟，和10個年齡相匹未感染的對照肺，進行了比較。使用七色免疫組織化學分析、顯微計算機斷層掃描成像、掃描電子顯微鏡、腐蝕鑄模和基因表達的直接多重測量研究了這些肺。
研究人員發現，在死於與Covid-19相關或與流感相關的呼吸衰竭的患者中，外周肺的組織學表現為瀰漫性肺泡損傷伴血管周圍T細胞浸潤。來自Covid-19患者的肺部也顯示出獨特的血管特徵，包括與細胞內病毒的存在和細胞膜破裂相關的嚴重內皮損傷。Covid-19患者的肺血管組織學分析顯示，廣泛的血栓形成並伴有微血管病變。Covid-19患者的肺泡毛細血管血栓發生率是流感患者的9倍（P<0.001）。在Covid-19患者的肺中，新血管的生長量（主要是通過填充性血管生成機制產生）是流感患者肺的2.7倍（P<0.001）。
據了解，進行性呼吸衰竭是Covid-19大流行的主要死亡原因。儘管人們對其病理生理學有廣泛興趣，但對死於Covid-19患者外周肺的相關形態和分子變化知之甚少。
附：英文原文
Title: Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19
Author: Maximilian Ackermann, M.D.,, Stijn E. Verleden, Ph.D.,, Mark Kuehnel, Ph.D.,, Axel Haverich, M.D.,, Tobias Welte, M.D.,, Florian Laenger, M.D.,, Arno Vanstapel, Ph.D.,, Christopher Werlein, M.D.,, Helge Stark, Ph.D.,, Alexandar Tzankov, M.D.,, William W. Li, M.D.,, Vincent W. Li, M.D.,, Steven J. Mentzer, M.D.,, and Danny Jonigk, M.D.
Issue&Volume: 2020-05-21
Abstract: 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.
DOI: 10.1056/NEJMoa2015432
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2015432