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[2019冠状病毒病(COVID-19)十例患者经尸体针吸尸检脾脏的病理变化]

[Pathological changes of the spleen in ten patients with coronavirus disease 2019(COVID-19) by postmortem needle autopsy].

作者信息

Xu X, Chang X N, Pan H X, Su H, Huang B, Yang M, Luo D J, Weng M X, Ma L, Nie X

机构信息

Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Zhonghua Bing Li Xue Za Zhi. 2020 Jun 8;49(6):576-582. doi: 10.3760/cma.j.cn112151-20200401-00278.

DOI:10.3760/cma.j.cn112151-20200401-00278
PMID:32340089
Abstract

To study the pathological changes of the spleen in patients with COVID-19 and to analyze the relationship between the weakened immune system and splenic lesions. Postmortem needle autopsies from the spleen were carried out on 10 patients who died from COVID-19 in Wuhan. Routine hematoxylin and eosin (HE) staining was used to observe the pathological changes. The changes of lymphocytes were studied further with immunohistochemistry.RT-PCR was used to detect 2019-nCoV RNA in the spleen. In addition,the Epstein-Barr virus (EBV) was detected by in situ hybridization, and coronavirus particles were detected by transmission electron microscopy in 2 cases. There were 7 males and 3 females, with an average age of 68.3 years.Of the 10 cases, 4 had cancer history and another 4 had other underlying diseases respectively.Cough, fever, malaise and dyspnea were the main clinical symptoms.The time from onset to death was 15-45 days.Ten cases patients had normal or slight increase in peripheral blood leukocyte count in the early stage of the disease, 6 cases had significant increase before death. Five patients' peripheral blood lymphocyte count decreased in the early stage of the disease, and 10 patients' peripheral blood lymphocyte count decreased significantly before the disease progressed or died. Seven cases were treated with corticosteroid (methylprednisolone ≤40 mg/d, not more than 5 days). Histopathological examination showed that the cell composition of the spleen decreased, white pulp atrophied at different levels, meanwhile lymphoid follicles decreased or absent;in addition, the ratio of red pulp to white pulp increased with varying degrees. In 7 cases, more neutrophil infiltration was found, and in 5 cases, scattered plasma cell infiltration was found. Macrophage proliferation and hemophagocytic phenomena in a few cells were found in a case. Meanwhile, necrosis and lymphocyte apoptosis were detected in 2 cases, small artery thrombosis and spleen infarction in 1 case, and fungal infection in 1 case. The results of immunohistochemistry showed that the T and B lymphocyte components of the spleen in all cases decreased in varying degrees. CD20(+) B cells were found to accumulate in the lymphoid sheath around the splenic artery in 8 cases. However, CD20 and CD21 immunostaining in 2 cases showed that the number of white pulp was almost normal, and splenic nodules were atrophic. CD3(+), CD4(+) and CD8(+)T cells were decreased. In 9 cases,CD68(+) macrophages were no significant changes in the distribution and quantity. While more CD68(+) cells were found in the medullary sinuses of 1 case (related to fungal infection). Few CD56(+) cells were found. EBV was negative by in situ hybridization. RT-PCR was used to detect the nucleic acid of 2019-nCoV. One of 10 cases was positive, 39 years old,who was the youngest patient in this group, and the other 9 cases were negative. Coronavirus particles were found in the cytoplasm of macrophage under electron microscope in 2 cases. The death of COVID-19 occurs mainly in the elderly, and some cases have no underlying diseases. Spleen may be one of the organs directly attacked by the virus in some patients who died from COVID-19. T and B lymphocyte in the spleen decrease in varying degrees, lymphoid follicles are atrophied, decreased or absent, and the number of NK cells do not change significantly. And the pathological changes of the spleen are not related to the use of low dose corticosteroid, which may be related to the direct attack of virus and the attack of immune system on its own tissues.

摘要

研究新型冠状病毒肺炎(COVID-19)患者脾脏的病理变化,分析免疫系统减弱与脾脏病变之间的关系。对武汉10例死于COVID-19的患者进行脾脏针吸尸检。采用常规苏木精-伊红(HE)染色观察病理变化。用免疫组织化学进一步研究淋巴细胞的变化。采用逆转录聚合酶链反应(RT-PCR)检测脾脏中的2019-nCoV RNA。此外,通过原位杂交检测爱泼斯坦-巴尔病毒(EBV),并对2例患者用透射电子显微镜检测冠状病毒颗粒。患者中男性7例,女性3例,平均年龄68.3岁。10例患者中,4例有癌症病史,另4例分别有其他基础疾病。咳嗽、发热、乏力和呼吸困难为主要临床症状。从发病到死亡时间为15~45天。10例患者疾病早期外周血白细胞计数正常或轻度升高,6例患者死亡前显著升高。5例患者疾病早期外周血淋巴细胞计数下降,10例患者疾病进展或死亡前外周血淋巴细胞计数显著下降。7例患者接受了糖皮质激素治疗(甲泼尼龙≤40mg/d,不超过5天)。组织病理学检查显示,脾脏细胞成分减少,白髓不同程度萎缩,同时淋巴滤泡减少或消失;此外,红髓与白髓比例不同程度增加。7例可见较多中性粒细胞浸润,5例可见散在浆细胞浸润。1例可见巨噬细胞增生及少数细胞噬血现象。同时,2例检测到坏死及淋巴细胞凋亡,1例检测到小动脉血栓形成及脾梗死,1例检测到真菌感染。免疫组织化学结果显示,所有病例脾脏的T和B淋巴细胞成分均不同程度减少。8例可见CD20(+)B细胞在脾动脉周围淋巴鞘中积聚。然而,2例CD20和CD21免疫染色显示白髓数量几乎正常,脾小结萎缩。CD3(+)、CD4(+)和CD8(+)T细胞减少。9例CD68(+)巨噬细胞在分布和数量上无明显变化。而1例患者髓窦中发现较多CD68(+)细胞(与真菌感染有关)。发现少数CD56(+)细胞。原位杂交EBV为阴性。用RT-PCR检测2019-nCoV核酸。10例中有1例阳性,39岁,为该组最年轻患者,其余9例为阴性。2例在电子显微镜下巨噬细胞胞质中发现冠状病毒颗粒。COVID-19死亡主要发生在老年人,部分病例无基础疾病。脾脏可能是部分死于COVID-19患者中病毒直接攻击的器官之一。脾脏中T和B淋巴细胞不同程度减少,淋巴滤泡萎缩、减少或消失,自然杀伤(NK)细胞数量无明显变化。脾脏的病理变化与低剂量糖皮质激素的使用无关,可能与病毒直接攻击及免疫系统对自身组织的攻击有关。

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