《免疫》：COVID-19可导致严重的大脑炎症

资讯作者：Albert Ludwigs University of Freiburg

编辑翻译：奇奇

译文校对：菁菁

本文献于2021年6月发表在美国医学学术期刊《免疫》（Immunity）上。文中美国弗莱堡大学医学院的研究人员发现，COVID-19患者的中枢神经系统可能产生了严重的炎症反应，并涉及到血管系统和大脑组织周围的多种不同免疫细胞。

在感染冠状病毒SARS-CoV-2期间和之后，患者可能会出现严重的神经系统症状，包括与COVID-19相关的味觉和嗅觉丧失。除了病毒造成的直接损害外，研究人员还猜测过度炎症反应在这种疾病中也有影响。来自弗莱堡大学医学中心和卓越集群CIBSS的一组研究人员发现，COVID-19患者的中枢神经系统可能产生了严重的炎症反应，这涉及到血管系统和大脑组织周围的不同免疫细胞。由神经病理学研究所医学主任Marco Prinz教授和内科学II肝消化学转化系统免疫学主任Bertram Bengsch教授领导的团队在最新一期的《免疫》杂志上发表了他们的研究结果。

主要作者Henrike Salié说：“尽管已经有证据表明COVID-19涉及中枢神经系统，但大脑炎症的程度还是令我们感到惊讶。”另一位主要作者Dr. Marius Schwabenland也解释道：“特别是我们检测到了许多健康大脑中没有的小胶质细胞瘤。”研究人员使用一种新的测量方法（即流式细胞术成像）能够确定不同的细胞类型，以及病毒感染的细胞和它们的空间相互作用，这些细节详情都是之前未曾注意到的。

破坏大脑的免疫反应

Prinz说：“到目前为止，人们对COVID-19的炎症模式知道的很少。与其他炎症性脑疾病相比，COVID-19引发的炎症反应是独一无二的，是大脑免疫反应严重紊乱的表现。特别是小胶质细胞（作为大脑的基本防御细胞）被强烈地激活，我们还观察到杀伤性T细胞的迁移以及脑干中明显地神经系统炎症的发展。”他的研究曾在2020年获得莱布尼茨奖（德国科研最高奖）。

Bengsch还补充说：“在小脑血管附近的免疫变化尤其明显。在这些区域，病毒受体ACE2被表达，冠状病毒可以进入这些区域，而且在那里也可以直接检测到病毒。免疫细胞能够识别那里受感染的细胞，然后炎症会扩散到神经组织，引起症状。”

免疫学、病毒学和神经病理学研究

弗莱堡医学中心内科 II 医学主任、弗莱堡大学医学院教务副院长Robert Thimme教授强调，高水平的科学专业知识和不同研究团队间出色的合作是在大流行期间迅速获得知识的必要前提。“弗莱堡医学中心的核心优势是使用最先进的方法进行以患者为导向的免疫学、病毒学和神经病理学研究。该研究展示了我们在弗莱堡如何通过出色的研究来帮助了解冠状病毒大流行中的疾病过程。虽然我们已经知道从冠状病毒感染中恢复需要强大的免疫反应，但是错误的免疫反应明显会造成严重损害。”

英语原文  

COVID-19 Can Cause Severe Inflammation in the Brain

Both during and after infection with the Coronavirus SARS-CoV-2, patients may suffer from severe neurological symptoms, including anosmia, the loss of taste and smell typically associated with COVID-19. Along with direct damage caused by the virus, researchers suspect a role for excessive inflammatory responses in the disease. A team of researchers from the Freiburg University Medical Center and the Cluster of Excellence CIBSS has shown that a severe inflammatory response can develop in the central nervous system of COVID-19 patients involving different immune cells around the vascular system and in the brain tissue. The team led by Professor Dr. Marco Prinz, Medical Director at the Institute of Neuropathology, and Professor Dr. Bertram Bengsch, Section Head of Translational Systems Immunology at the Internal Medicine II just published their results in the current issue of Immunity.

"Even though there was already evidence of central nervous system involvement in COVID-19, the extent of inflammation in the brain surprised us," says lead author Henrike Salié. "In particular the many microglial nodules we detected cannot usually be found in the healthy brain," comments lead author Dr. Marius Schwabenland. Using a novel measurement method, imaging mass cytometry, they were able to determine different cell types as well as virus-infected cells and their spatial interaction in previously unseen detail.

Disruption of the brain's immune response

"Until now, the inflammatory pattern in COVID-19 was poorly understood. Even compared to other inflammatory brain diseases, the inflammatory responses triggered by COVID-19 are unique and indicate a severe disturbance of the brain's immune response. In particular, the essential defense cells of the brain, known as microglial cells, are particularly strongly activated, and we also observed migration of T-killer cells and development of a pronounced neuroinflammation in the brain stem," says Prinz, who received the Leibniz Prize in 2020 for his research.

"The immune changes are particularly detectable near small brain vessels. In these areas, the viral receptor ACE2 is expressed, onto which the coronavirus can dock, and the virus was also directly detectable there," Bengsch adds," The immune cells recognize infectedcells there and that inflammation then spreads to the nerve tissue, causing symptoms.

Immunological, virological, and neuropathological research

Professor Dr. Robert Thimme, Medical Director of Internal Medicine II at the Freiburg Medical Center and Vice Deanfor Academic Affairs of the University of Freiburg Medical Faculty, emphasizes how high levels of scientific expertise and excellent cooperation between different research teams is a basic prerequisite for rapid knowledge gain in the pandemic. "Patient-oriented immunological, virological, and neuropathological research using state-of-the-art methods is a core strength at the Freiburg Medical Center. This study shows how we can contribute to understanding the disease processes in the Coronavirus pandemic through excellent research in Freiburg. While we already knew that a strong immune response is needed for recovery from Coronavirus infection, apparently a misdirected immune response can cause severe damage."

参考文献 

Marius Schwabenland et al, Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T cell interactions, Immunity (2021).

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