IRCCS Mondino Foundation, Pavia, Italy.
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Eur J Neurol. 2021 Nov;28(11):3856-3865. doi: 10.1111/ene.15045. Epub 2021 Aug 17.
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 χ 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.
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 患者的神经症状与脑病理学发现之间的相关性仍知之甚少。
我们对 COVID-19 的神经病理学研究进行了系统的文献回顾，包括截至 2021 年 4 月 22 日发表的 45 篇文章中的 438 名患者。我们检索了关于人口统计学、临床和神经病理学发现的定量数据。我们基于不同的临床和脑病理学特征，通过 Wilcoxon 秩和检验或 χ 检验比较患者的亚组。
COVID-19 患者的神经病理学发现包括小胶质细胞增生（52.5%）、星形胶质细胞增生（45.6%）、炎症浸润（44.0%）、缺氧缺血性病变（40.8%）、水肿（25.3%）和出血性病变（20.5%）。分别有 41.9%和 28.3%的患者脑组织中检测到 SARS-CoV-2 RNA 和蛋白。245 名患者（55.9%）提供了详细的临床信息，其中 96 名患者（39.2%）在出现典型 COVID-19 表现的同时出现了神经症状。我们发现：（i）有神经症状与无神经症状的患者的脑组织中 SARS-CoV-2 RNA 和蛋白的检出率无差异；（ii）脑水肿、缺氧缺血性病变和炎症浸润在有神经功能障碍的患者中更为常见；（iii）老年患者更常出现神经症状。
我们对 COVID-19 临床相关性的系统综述强调了脑炎症反应和缺氧缺血性损伤的发病相关性，而不是神经元病毒载量。这项分析表明，需要更有针对性的研究设计，特别是从潜在治疗试验的角度来看。
