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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Abstract

BACKGROUND: 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.

METHODS: We performed a systematic literature review on neuropathological studies in COVID-19, including 438 patients from 45 papers published by April 22, 2021. We retrieved quantitative data regarding demographic, clinical and neuropathological findings. We carried out Wilcoxon rank-sum test or chi-square test to compare patients' subgroups based on different clinical and brain pathology features.

RESULTS: 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) detection rate of SARS-CoV-2 RNA and proteins in brain specimens did not differ between patients with vs. 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.

CONCLUSIONS: 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.

Original languageEnglish
JournalEuropean Journal of Neurology
DOIs
Publication statusE-pub ahead of print - Aug 2 2021

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