Yao X H, Li T Y, He Z C, Ping Y F, Liu H W, Yu S C, Mou H M, Wang L H, Zhang H R, Fu W J, Luo T, Liu F, Guo Q N, Chen C, Xiao H L, Guo H T, Lin S, Xiang D F, Shi Y, Pan G Q, Li Q R, Huang X, Cui Y, Liu X Z, Tang W, Pan P F, Huang X Q, Ding Y Q, Bian X W
Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Department of Vascular Surgery, Southwest Hospital, Third Military MedicalUniversity (Army Medical University), Chongqing 400038, China.
Zhonghua Bing Li Xue Za Zhi. 2020 May 8;49(5):411-417. doi: 10.3760/cma.j.cn112151-20200312-00193.
To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.
为研究新型冠状病毒(2019 - nCoV)感染肺炎(世界卫生组织命名为2019冠状病毒病,COVID - 19)的病理特征及临床意义。对中国重庆3例死于新型冠状病毒肺炎的患者进行了肺、心、肾、脾、骨髓、肝、胰、胃、肠、甲状腺及皮肤的微创尸检。采用苏木精 - 伊红染色(HE)、透射电子显微镜及组织化学染色观察上述器官或组织的病理变化。进行免疫组织化学染色评估免疫细胞浸润情况及2019 - nCoV蛋白表达。采用实时荧光定量PCR检测2019 - nCoV的RNA。观察到肺泡结构出现多种损伤,伴有少量浆液渗出和纤维蛋白渗出。部分肺泡可见透明膜形成。肺泡内浸润的免疫细胞主要为巨噬细胞和单核细胞。还观察到中度多核巨细胞、少量淋巴细胞、嗜酸性粒细胞和中性粒细胞。浸润的淋巴细胞大多为CD4阳性T细胞。还显示Ⅱ型肺泡上皮细胞显著增生及肺泡上皮细胞局灶性脱落。肺泡间隔血管充血、水肿、增宽,有单核细胞和淋巴细胞轻度浸润。少数微血管内可见透明血栓。肺组织可见局灶性出血、部分肺泡腔内渗出物机化及肺间质纤维化。部分支气管上皮脱落。电镜下在支气管黏膜上皮及Ⅱ型肺泡上皮内观察到冠状病毒颗粒。免疫组织化学染色显示部分肺泡上皮及巨噬细胞2019 - nCoV抗原呈阳性。实时荧光定量PCR分析鉴定出2019 - nCoV核酸阳性信号。脾脏观察到淋巴细胞数量减少、细胞变性及坏死。此外,在其他器官和组织观察到实质细胞变性和坏死、小血管内透明血栓形成及慢性疾病的病理改变,但这些器官未观察到冠状病毒感染证据。新型冠状病毒肺炎患者的肺部表现出明显的病理损害,包括肺泡渗出性炎症和间质性炎症、肺泡上皮细胞增生及透明膜形成。虽然2019 - nCoV主要分布于肺,但感染还累及心脏、血管、肝脏、肾脏及其他器官。有必要进一步研究该疾病病理变化的潜在机制。