Department of Pathology, Amsterdam University Medical Centers (UMC), VU University Amsterdam, Amsterdam, Netherlands.
Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Lancet Microbe. 2020 Nov;1(7):e290-e299. doi: 10.1016/S2666-5247(20)30144-0. Epub 2020 Sep 25.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy.
This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course.
Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78). Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets..
In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19.
Amsterdam UMC Corona Research Fund.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）靶向多个器官并导致严重的凝血功能障碍。组织病理学器官变化不仅归因于直接的病毒诱导作用，还归因于免疫反应。本研究的目的是评估病毒存在的持续时间，确定炎症反应的程度，并研究凝血功能障碍的根本原因。
这是一项在荷兰阿姆斯特丹大学医学中心（UMC）进行的前瞻性尸检队列研究。征得亲属同意后，对 21 名因 COVID-19 要求进行尸检的患者进行了全身尸检，这些患者的尸检时间为 2020 年 3 月 9 日至 5 月 18 日之间。除了对器官损伤进行组织病理学评估外，还评估了 SARS-CoV-2 核衣壳蛋白的存在以及免疫浸润物和血栓的组成，并将所有这些都与疾病过程相关联。
我们的队列（n=21）包括 16 名（76%）男性，中位年龄为 68 岁（范围 41-78 岁）。中位疾病病程（从症状发作到死亡的时间）为 22 天（范围 5-44 天）。在 11 名接受 SARS-CoV-2 嗜性检测的患者中，SARS-CoV-2 感染细胞存在于多个器官中，在肺部最为丰富，但随着疾病病程的延长，肺部的 SARS-CoV-2 感染细胞变得稀少。其他 SARS-CoV-2 阳性器官包括上呼吸道、心脏、肾脏和胃肠道。在对 9 至 21 名患者/器官的组织进行的器官组织学分析中，肺部、心脏、肝脏、肾脏和大脑均存在广泛的炎症反应。在大脑中，嗅球和延髓中可见广泛的炎症。在肺部、心脏、肾脏、肝脏、脾脏和大脑中均可见血栓和嗜中性粒细胞栓子，并且在疾病后期（15 例有血栓，病程中位数 22 天[5-44]；10 例有嗜中性粒细胞栓子，病程 21 天[5-44]）最常观察到。嗜中性粒细胞栓子有两种形式：仅由嗜中性粒细胞和细胞外陷阱（NETs）组成，或由 NETs 和血小板组成的聚集物。
在患有致命 COVID-19 的患者中，存在广泛的全身炎症反应，同时持续存在嗜中性粒细胞和 NETs。然而，在 COVID-19 的晚期仅偶尔存在 SARS-CoV-2 感染细胞。这表明存在适应性免疫反应不良，并证实免疫调节是治疗严重 COVID-19 的目标。
阿姆斯特丹 UMC 科罗娜研究基金。
