Institute of Forensic Medicine, Jena University Hospital, Jena, Germany.
Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany.
Histopathology. 2021 Apr;78(5):727-737. doi: 10.1111/his.14281. Epub 2020 Dec 18.
Haemophagocytosis in the bone marrow of patients who have succumbed to coronavirus disease 19 (COVID-19) has not been widely studied. The aims of the present study were to perform morphological analyses and morphometry of haemophagocytosis in the bone marrow of patients with severe COVID-19, and to correlate the findings with the clinical course of the disease.
In this single-centre study performed at the University Hospital Jena, bone marrow specimens of 15 deceased patients who had experienced a severe course of COVID-19 were sampled from the vertebral column during autopsy. Slides of the bone marrow were stained with routine stains or immunohistochemically, and further examined for haemophagocytosis by the use of light microscopy. To substantiate the morphological findings, additional slides were stained for CD163 and morphometry was performed. In all bone marrow samples, an increase in cellularity was found. Haemophagocytes with erythrophagocytosis were detected in 67% of the deceased patients. In tissues with low numbers of haemophagocytes or ill-defined haemophagocytes, an increase in iron deposits was frequently seen. Morphological findings were then correlated with several important clinical data, and the HScore (probability of having a reactive hemophagocytic syndrome) was calculated to posthumously confirm the diagnosis of secondary haemophagocytic lymphohistiocytosis. The median duration of disease and the hospitalisation time were lower in patients with haemophagocytosis (n = 10) than in patients without haemophagocytosis (n = 5). In addition, patients with haemophagocytes showed increased inflammatory parameters 2-5 days prior to death, in contrast to patients without haemophagocytes.
Haemophagocytosis is a common finding in the bone marrow of deceased individuals with severe COVID-19, and may indicate fatal severe acute respiratory syndrome coronavirus 2 infections.
在因 2019 年冠状病毒病(COVID-19)而死亡的患者的骨髓中,噬血细胞现象尚未得到广泛研究。本研究的目的是对重症 COVID-19 患者的骨髓中噬血细胞进行形态学分析和形态计量学研究,并将这些发现与疾病的临床过程相关联。
在耶拿大学医院进行的这项单中心研究中,对 15 名经历过严重 COVID-19 病程的死亡患者的脊柱进行尸检,从这些患者的脊柱中采集骨髓标本。对骨髓切片进行常规染色或免疫组织化学染色,并使用光学显微镜进一步检查噬血细胞。为了证实形态学发现,还对另外的切片进行了 CD163 染色和形态计量学检查。在所有的骨髓样本中,均发现细胞增多。在 67%的死亡患者中检测到了具有红细胞吞噬作用的噬血细胞。在噬血细胞数量较少或噬血细胞定义不明确的组织中,经常可见铁沉积增加。然后将形态学发现与一些重要的临床数据相关联,并计算 H 评分(发生反应性噬血细胞性综合征的可能性),以死后确认继发性噬血细胞性淋巴组织细胞增生症的诊断。在有噬血细胞(n=10)的患者中,疾病持续时间和住院时间中位数均低于无噬血细胞(n=5)的患者。此外,与无噬血细胞的患者相比,有噬血细胞的患者在死亡前 2-5 天表现出更高的炎症参数。
噬血细胞是重症 COVID-19 死亡患者骨髓中的常见发现,可能表明致命的严重急性呼吸综合征冠状病毒 2 感染。