Neuropathology of patients with COVID-19 in Germany: a post-mortem case series.
Neuropathology of patients with COVID-19 in Germany: a post-mortem case series.
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DOI：
10.1016/s1474-4422(20)30308-2
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Glatzel M
中科院分区：
文献类型：
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作者：
Matschke J;Lütgehetmann M;Hagel C;Sperhake JP;Schröder AS;Edler C;Mushumba H;Fitzek A;Allweiss L;Dandri M;Dottermusch M;Heinemann A;Pfefferle S;Schwabenland M;Sumner Magruder D;Bonn S;Prinz M;Gerloff C;Püschel K;Krasemann S;Aepfelbacher M;Glatzel M
COVID-19的突出临床症状包括CNS表现。然而，目前尚不清楚COVID-19的病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是否能够进入CNS，以及是否会引起神经病理学变化。我们研究了死于COVID-19的患者的脑组织的神经胶质反应，炎症变化以及CNS中SARS-CoV-2的存在。在这个尸检病例系列中，我们调查了2020年3月13日至4月24日期间在德国汉堡死亡的患者大脑中的神经病理学特征。入选标准包括通过定量RT-PCR（qRT-PCR）对SARS-CoV-2的阳性检测和足够样本的可用性。我们做了神经病理学检查，包括组织学染色和免疫组化染色的活化星形胶质细胞，活化小胶质细胞，细胞毒性T淋巴细胞在嗅球，基底神经节，脑干和小脑。此外，我们通过qRT-PCR和免疫组织化学在选定的患者和大脑区域中研究了SARS-CoV-2的存在和定位。我们的研究纳入了43例患者。患者在医院、疗养院或家中死亡，年龄在51 - 94岁之间（中位数76岁[IQR 70 - 86]）。我们发现新鲜的领土缺血性病变6例（14%）。37例（86%）患者在所有评估区域均存在星形胶质细胞增生。小胶质细胞活化和细胞毒性T淋巴细胞浸润在脑干和小脑最明显，34例（79%）患者出现脑膜细胞毒性T淋巴细胞浸润。在40名接受检查的患者中，有21名（53%）的大脑中可以检测到SARS-CoV-2，在起源于下脑干的颅神经和脑干的分离细胞中发现了SARS-CoV-2病毒蛋白。CNS中SARS-CoV-2的存在与神经病理学改变的严重程度无关。总体而言，COVID-19患者的神经病理学变化似乎较轻，脑干明显的神经炎症变化是最常见的发现。没有证据表明SARS-CoV-2直接导致CNS损伤。这些结果的普遍性需要在未来的研究中进行验证，因为病例数量和临床数据的可用性较低，并且未纳入年龄匹配和性别匹配的对照。德国研究基金会，联邦汉堡州，欧盟（eRARE），德国感染研究中心（DZIF）。
Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).