Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Division of Pathology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
Histol Histopathol. 2023 Jun;38(6):623-636. doi: 10.14670/HH-18-557. Epub 2022 Dec 1.
In COVID-19 pneumonia, early detection and appropriate treatment are essential to prevent severe exacerbation. Therefore, it is important to understand the initiating events of COVID-19 pneumonia. However, at present, the literature about early stage disease has been very limited. Here, we investigated the earliest histopathological changes and gene expression profiles associated with COVID-19 pneumonia.
We carefully examined 25 autopsied cases with different clinical courses. Dilation of capillaries and edematous thickening of the alveolar septa were found even in areas that macroscopically looked almost normal. Pneumocytes, histocytes/macrophages, and vascular endothelial cells were immunohistochemically positive for tissue factor, which is an important early responder to tissue injuries. Comprehensive gene expression analyses revealed that those lesions presented differential profiles compared to those of control lungs and were associated with a significant upregulation of the lysosomal pathway.
Alveolar capillary dilation and edematous thickening may be the earliest histopathological change detected in COVID-19 pneumonia. Intensive investigations of such lesions may lead to an understanding of the initiating event of not only COVID-19 pneumonia but also of general diffuse alveolar damage.
在 COVID-19 肺炎中，早期检测和适当治疗对于预防严重恶化至关重要。因此，了解 COVID-19 肺炎的起始事件非常重要。然而，目前关于疾病早期阶段的文献非常有限。在这里，我们研究了与 COVID-19 肺炎相关的最早的组织病理学变化和基因表达谱。
我们仔细检查了 25 例具有不同临床病程的尸检病例。即使在宏观上看起来几乎正常的区域，也发现了毛细血管扩张和肺泡隔水肿增厚。组织因子的免疫组织化学染色呈阳性，组织因子是组织损伤的重要早期应答因子，肺泡细胞、组织细胞/巨噬细胞和血管内皮细胞呈阳性。综合基因表达分析显示，与对照肺相比，这些病变具有不同的特征，并与溶酶体途径的显著上调相关。
肺泡毛细血管扩张和水肿增厚可能是 COVID-19 肺炎最早的组织病理学变化。对这些病变的深入研究可能不仅有助于理解 COVID-19 肺炎的起始事件，还可能有助于理解一般弥漫性肺泡损伤的起始事件。
