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.).

中文翻译：

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Covid-19 中的肺血管内皮炎、血栓形成和血管生成。

背景 进行性呼吸衰竭是 2019 年冠状病毒病 (Covid-19) 大流行中的主要原因。尽管人们对该疾病的病理生理学产生了广泛的兴趣，但人们对死于 Covid-19 的患者周围肺的相关形态和分子变化知之甚少。方法 我们检查了尸检过程中从死于 Covid-19 的患者身上获得的 7 个肺，并将其与尸检过程中从死于甲型 H1N1 流感继发急性呼吸窘迫综合征 (ARDS) 的患者身上获得的 7 个肺以及 10 名年龄匹配的患者进行了比较。 ，未感染的对照肺。使用七色免疫组织化学分析、微型计算机断层扫描成像、扫描电子显微镜、腐蚀铸件和基因表达的直接多重测量对肺部进行研究。结果 在死于 Covid-19 相关或流感相关呼吸衰竭的患者中，周围肺的组织学模式是弥漫性肺泡损伤，伴有血管周围 T 细胞浸润。Covid-19患者的肺部也表现出独特的血管特征，包括与细胞内病毒的存在和细胞膜破裂相关的严重内皮损伤。Covid-19 患者肺血管的组织学分析显示，存在广泛的血栓形成并伴有微血管病变。Covid-19 患者的肺泡毛细血管微血栓发生率是流感患者的 9 倍（P<0.001）。在 Covid-19 患者的肺部，新血管生长量（主要通过套叠性血管生成机制）是流感患者肺部的 2.7 倍（P<0.001）。结论 在我们的小型系列研究中，血管生成将 Covid-19 的肺部病理学与同样严重的流感病毒感染的肺部病理学区分开来。我们的观察结果的普遍性和临床意义需要进一步的研究来确定。（由美国国立卫生研究院和其他机构资助）。