Department of Pathology, University Vita-Salute, Milan and San Raffaele Scientific Institute, Milan, Italy.
Pulmonology Unit, Thoracic Diseases Department, G.B. Morgagni Hospital, Forlì, Italy,
Respiration. 2021;100(6):488-498. doi: 10.1159/000514822. Epub 2021 Mar 16.
The pathogenetic steps leading to Covid-19 interstitial pneumonia remain to be clarified. Most postmortem studies to date reveal diffuse alveolar damage as the most relevant histologic pattern. Antemortem lung biopsy may however provide more precise data regarding the earlier stages of the disease, providing a basis for novel treatment approaches.
To ascertain the morphological and immunohistochemical features of lung samples obtained in patients with moderate Covid-19 pneumonia.
Transbronchial lung cryobiopsy was carried out in 12 Covid-19 patients within 20 days of symptom onset.
Histopathologic changes included spots of patchy acute lung injury with alveolar type II cell hyperplasia, with no evidence of hyaline membranes. Strong nuclear expression of phosphorylated STAT3 was observed in >50% of AECII. Interalveolar capillaries showed enlarged lumen and were in part arranged in superposed rows. Pulmonary venules were characterized by luminal enlargement, thickened walls, and perivascular CD4+ T-cell infiltration. A strong nuclear expression of phosphorylated STAT3, associated with PD-L1 and IDO expression, was observed in endothelial cells of venules and interstitial capillaries. Alveolar spaces macrophages exhibited a peculiar phenotype (CD68, CD11c, CD14, CD205, CD206, CD123/IL3AR, and PD-L1).
Morphologically distinct features were identified in early stages of Covid-19 pneumonia, with epithelial and endothelial cell abnormalities different from either classical interstitial lung diseases or diffuse alveolar damage. Alveolar type II cell hyperplasia was a prominent event in the majority of cases. Inflammatory cells expressed peculiar phenotypes. No evidence of hyaline membranes and endothelial changes characterized by IDO expression might in part explain the compliance and the characteristic pulmonary vasoplegia observed in less-advanced Covid-19 pneumonia.
导致 COVID-19 间质性肺炎的发病步骤仍有待阐明。迄今为止，大多数尸检研究揭示弥漫性肺泡损伤是最相关的组织学模式。然而，生前肺活检可能提供有关疾病早期阶段的更精确数据，为新的治疗方法提供依据。
确定中度 COVID-19 肺炎患者肺样本的形态学和免疫组织化学特征。
在症状发作后 20 天内对 12 例 COVID-19 患者进行经支气管肺冷冻活检。
组织病理学变化包括局灶性斑片状急性肺损伤，伴有肺泡 II 型细胞增生，无透明膜证据。超过 50%的 AECII 中观察到磷酸化 STAT3 的强核表达。肺泡毛细血管腔扩大，部分呈重叠排列。肺小静脉表现为管腔扩大、壁增厚和血管周围 CD4+T 细胞浸润。小静脉和间质毛细血管内皮细胞中观察到磷酸化 STAT3 的强核表达，与 PD-L1 和 IDO 表达相关。肺泡腔巨噬细胞表现出独特的表型（CD68、CD11c、CD14、CD205、CD206、CD123/IL3AR 和 PD-L1）。
在 COVID-19 肺炎的早期阶段确定了形态学上不同的特征，上皮和内皮细胞异常与经典间质性肺疾病或弥漫性肺泡损伤不同。大多数情况下，II 型肺泡细胞增生是一个突出的事件。炎症细胞表达独特的表型。无透明膜和内皮细胞改变的证据，其特征是 IDO 表达，可能部分解释了在不太严重的 COVID-19 肺炎中观察到的顺应性和特征性肺血管舒张。
