Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients
Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients
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DOI：
10.1016/j.ebiom.2020.102833
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发表时间：
2020-07-01
期刊：
影响因子：
11.1
通讯作者：
Bian, Xiu-Wu
中科院分区：
文献类型：
--
作者：
Wang, Chaofu;Xie, Jing;Bian, Xiu-Wu
背景：由严重急性呼吸综合征冠状病毒2（SARS - CoV - 2）感染引起的新型冠状病毒肺炎（COVID - 19）可导致一系列临床症状和重症，包括急性呼吸窘迫综合征（ARDS）和致命的器官衰竭。我们报告了对死亡病例的肺和其他器官进行的基础病理学研究，以从机制上理解重症COVID - 19，并为这些病例开发特异性治疗方法。
方法：对两例COVID - 19死亡病例的尸体进行了尸检和标本的病理学研究。对每位患者进行了大体解剖以及苏木精 - 伊红（HE）染色的组织学研究。对肺组织进行了阿尔辛蓝/过碘酸 - 希夫（AB - PAS）染色和马松染色，以检查黏液、纤维蛋白和胶原纤维。对两名患者的肺组织切片进行了免疫组织化学染色。进行实时聚合酶链反应（PCR）以检测SARS - CoV - 2的感染。进行流式细胞术分析以检测S蛋白的直接结合以及巨噬细胞细胞表面血管紧张素转换酶2（ACE2）的表达。
发现：肺的主要病理特征包括I型肺泡上皮细胞广泛受损和II型肺泡细胞非典型增生，伴有透明膜形成、局灶性出血、渗出和肺水肿以及肺实变。肺泡内伴有纤维蛋白渗出物的黏液栓以及肺泡巨噬细胞功能障碍是特征性异常。肺泡和肺门淋巴组织中的II型肺泡上皮细胞和巨噬细胞被SARS - CoV - 2感染。SARS - CoV - 2的S蛋白通过S蛋白 - ACE2相互作用直接与巨噬细胞结合。
解释：SARS - CoV - 2对肺泡巨噬细胞的感染可能是“细胞因子风暴”的驱动因素，这可能导致肺组织、心肺损伤，并导致多器官衰竭。
Background: The novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a series of clinical symptoms and severe illnesses, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases.Methods: The autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining was performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages.Findings: The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction.Interpretation: Infection of alveolar macrophage by SARS-CoV-2 might be drivers of the "cytokine storm", which might result in damages in pulmonary tissues, heart and lung, and lead to the failure of multiple organs