The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms. In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry. All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed. All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia. Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.

中文翻译：

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COVID-19 中伴有补体激活和炎症的神经血管损伤。

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 导致急性和长期神经系统表现的潜在机制仍然不清楚。我们的目的是描述 2019 年冠状病毒病患者的神经病理学变化，并确定潜在的病理生理机制。在这项大脑尸检研究中，我们通过免疫组织化学表征了血管病理学、神经炎症变化以及细胞和体液免疫反应。在 2020 年 3 月至 2020 年 7 月的第一波大流行期间，所有患者均死亡。所有患者均为成年人，在感染持续时间较短后死亡，部分患者突然死亡，呼吸系统受累极少。SARS-CoV-2 感染在生前或死后检测中得到证实。对病理变化进行描述性分析，对浸润和血管变化进行定量分析。所有患者都有多灶性血管损伤，这是通过血清蛋白渗漏到脑实质中确定的。这伴随着广泛的内皮细胞激活。发现血小板聚集体和微血栓沿着血管腔粘附到内皮细胞上。在内皮细胞和血小板上发现了激活经典补体途径的免疫复合物。血管周围浸润主要由巨噬细胞和一些 CD8+ T 细胞组成。仅存在罕见的 CD4+ T 细胞和 CD20+ B 细胞。星形胶质细胞增生在血管周围区域也很突出。小胶质细胞结节在后脑中占主导地位，这与局灶性神经元丢失和神经吞噬症有关。针对内皮细胞的抗体介导的细胞毒性是最有可能导致血管渗漏、血小板聚集、神经炎症和神经元损伤的起始事件。应考虑针对免疫复合物的治疗方式。