[A pathological report of three COVID-19 cases by minimal invasive autopsies]

Zhonghua Bing Li Xue Za Zhi. 2020 May 8;49(5):411-417. doi: 10.3760/cma.j.cn112151-20200312-00193.
[Article in Chinese]

Abstract

Objective: 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). Methods: 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. Results: 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. Conclusions: 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.

目的: 研究新型冠状病毒(2019-nCoV)感染所致新型冠状病毒肺炎(WHO命名为2019冠状病毒病,COVID-19)病理学改变及其临床意义。 方法: 对重庆地区3例新型冠状病毒肺炎患者进行死亡后微创尸检,获取肺脏、心脏、肾脏、脾脏、骨髓、肝脏、胰腺、胃、肠、甲状腺和皮肤组织。常规HE、透射电镜和组织化学染色观察各脏器组织病理变化,免疫组织化学染色分析炎性细胞浸润情况和2019-nCoV病毒蛋白,荧光定量聚合酶链反应法检测各脏器中2019-nCoV病毒RNA。 结果: 肺泡结构呈现不同程度的破坏,肺泡腔内见少量浆液和纤维蛋白性渗出物,部分肺泡见透明膜形成。渗出细胞主要为单核细胞和巨噬细胞,可见少数多核巨细胞,淋巴细胞、嗜酸性粒细胞和中性粒细胞。淋巴细胞主要为CD4阳性T细胞。Ⅱ型肺泡上皮细胞显著增生,部分细胞脱落至肺泡腔。肺泡隔血管充血、水肿、增宽,可见少量单核细胞和淋巴细胞浸润,少数微血管内见透明血栓;肺组织灶性出血,部分肺泡腔渗出物机化和肺间质纤维化。肺内各级支气管黏膜均可见部分上皮脱落。电镜下小支气管以下气道黏膜上皮和Ⅱ型肺泡上皮细胞胞质内可见冠状病毒颗粒。免疫组织化学染色显示部分肺泡上皮和巨噬细胞呈2019-nCoV抗原阳性,荧光定量聚合酶链反应检测证实2019-nCoV核酸阳性。脾脏淋巴细胞减少,可见变性、坏死。其他器官组织病变包括不同程度的实质细胞变性、坏死、小血管内透明血栓形成,并见慢性基础疾病改变;均未观测到冠状病毒感染证据。 结论: 新型冠状病毒肺炎病变以肺最为显著,主要表现为肺泡渗出性炎和间质炎,肺泡上皮细胞增生和透明膜形成,病毒主要分布于肺,但该病还累及免疫器官、心血管、肝脏和肾脏等多个脏器受损。病变机制有待深入研究。.

Keywords: Autopsy; Coronavirus infections; Minimally invasive autopsy; Pathological conditions,anatomical.

Publication types

  • Case Reports

MeSH terms

  • Autopsy
  • Betacoronavirus / genetics
  • Betacoronavirus / isolation & purification
  • COVID-19
  • China
  • Coronavirus Infections* / pathology
  • Humans
  • Kidney / pathology
  • Liver / pathology
  • Lung / pathology*
  • Myocardium / pathology
  • Pandemics*
  • Pneumonia, Viral* / pathology
  • Real-Time Polymerase Chain Reaction
  • SARS-CoV-2
  • Skin / pathology
  • Thyroid Gland / pathology