Neuropathological findings from COVID-19 patients with neurological symptoms argue against a direct brain invasion of SARS-CoV-2: A critical systematic review.
Neuropathological findings from COVID-19 patients with neurological symptoms argue against a direct brain invasion of SARS-CoV-2: A critical systematic review.
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DOI：
10.1111/ene.15045
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发表时间：
2021-11
影响因子：
5.1
通讯作者：
Pisani A
中科院分区：
文献类型：
--
作者：
Cosentino G;Todisco M;Hota N;Della Porta G;Morbini P;Tassorelli C;Pisani A
神经病理学研究可以阐明与SARS-CoV-2感染相关的神经系统损伤机制。尽管关于这一主题的文献正在迅速增加，但COVID-19患者的神经系统症状和脑病理学发现之间的相关性在很大程度上仍然未知。我们对COVID-19的神经病理学研究进行了系统性文献综述，包括截至2021年4月22日发表的45篇文章中的438名患者。我们检索了有关人口统计学、临床和神经病理学结果的定量数据。我们进行了Wilcoxon秩和检验或χ2检验，以比较基于不同临床和脑病理学特征的患者亚组。COVID-19患者的神经病理学结果为小胶质细胞增生（52.5%）、星形胶质细胞增生（45.6%）、炎性浸润（44.0%）、缺氧缺血性病变（40.8%）、水肿（25.3%）和出血性病变（20.5%）。在41.9%和28.3%的受试者的脑标本中分别鉴定出SARS-CoV-2 RNA和蛋白质。245例患者（55.9%）提供了详细的临床信息，其中96例受试者（39.2%）出现了与典型COVID-19表现相关的神经系统症状。我们发现：（i）有神经系统症状的患者与无神经系统症状的患者脑标本中SARS-CoV-2 RNA和蛋白的检出率没有差异;（ii）脑水肿、缺氧缺血性病变和炎性浸润在有神经系统损伤的受试者中更常见;（iii）神经系统症状在老年人中更常见。我们对COVID-19临床相关性的系统性修订强调了脑炎症反应和缺氧缺血性损伤的致病相关性，而不是神经元病毒载量。这一分析表明，需要一个更有针对性的研究设计，特别是在潜在的治疗试验的角度。来自脑病理学的证据表明，水肿、缺氧缺血性病变、炎性浸润，而不是病毒RNA或蛋白质，与COVID-19患者的神经系统症状的存在相关，这证实了神经功能障碍可能是由于脑炎症和缺氧缺血性损伤，而不是由于SARS-CoV-2的直接细胞病变效应的假设。老年人在SARS-CoV-2感染的情况下可能表现出更高的神经系统表现风险。
Neuropathological studies can elucidate the mechanisms of nervous system damage associated with SARS‐CoV‐2 infection. Despite literature on this topic is rapidly expanding, correlations between neurological symptoms and brain pathology findings in COVID‐19 patients remain largely unknown. We performed a systematic literature review on neuropathological studies in COVID‐19, including 438 patients from 45 articles published by April 22, 2021. We retrieved quantitative data regarding demographic, clinical, and neuropathological findings. We carried out a Wilcoxon rank sum test or χ2 test to compare patients' subgroups based on different clinical and brain pathology features. Neuropathological findings in COVID‐19 patients were microgliosis (52.5%), astrogliosis (45.6%), inflammatory infiltrates (44.0%), hypoxic‐ischemic lesions (40.8%), edema (25.3%), and hemorrhagic lesions (20.5%). SARS‐CoV‐2 RNA and proteins were identified in brain specimens of 41.9% and 28.3% of subjects, respectively. Detailed clinical information was available from 245 patients (55.9%), and among them, 96 subjects (39.2%) had presented with neurological symptoms in association with typical COVID‐19 manifestations. We found that: (i) the detection rate of SARS‐CoV‐2 RNA and proteins in brain specimens did not differ between patients with versus those without neurological symptoms; (ii) brain edema, hypoxic‐ischemic lesions, and inflammatory infiltrates were more frequent in subjects with neurological impairment; (iii) neurological symptoms were more common among older individuals. Our systematic revision of clinical correlates in COVID‐19 highlights the pathogenic relevance of brain inflammatory reaction and hypoxic‐ischemic damage rather than neuronal viral load. This analysis indicates that a more focused study design is needed, especially in the perspective of potential therapeutic trials. The evidence from brain pathology that edema, hypoxic‐ischemic lesions, inflammatory infiltrates, but not viral RNA or proteins, are associated with the presence of neurological symptoms in COVID‐19 patients corroborates the hypothesis that neurological impairment is likely due to brain inflammatory and hypoxic‐ischemic damage rather than to the direct cytopathic effects of SARS‐CoV‐2. Older individuals could show a higher risk of neurological manifestations in the event of SARS‐CoV‐2 infection.
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DOI：
10.1016/s1474-4422(20)30308-2
发表时间：
2020-11
期刊：
The Lancet. Neurology
影响因子：
--
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
通讯作者：
Glatzel M
影响因子：
3.7
作者：
Moher D;Shamseer L;Clarke M;Ghersi D;Liberati A;Petticrew M;Shekelle P;Stewart LA;PRISMA-P Group
通讯作者：
PRISMA-P Group
影响因子：
34.7
作者：
Brown, Guy C.;Neher, Jonas J.
通讯作者：
Neher, Jonas J.
影响因子：
6.7
作者：
Meng, Yifan;Wu, Ping;Wu, Peng
通讯作者：
Wu, Peng
影响因子：
2
作者：
Fayed, Islam;Pivazyan, Gnel;Mai, Jeffrey C.
通讯作者：
Mai, Jeffrey C.