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. 2021 Nov;28(11):3856-3865.
doi: 10.1111/ene.15045. Epub 2021 Aug 17.

Neuropathological findings from COVID-19 patients with neurological symptoms argue against a direct brain invasion of SARS-CoV-2: A critical systematic review

Giuseppe Cosentino  1   2 , Massimiliano Todisco  1   2 , Noy Hota  2 , Giovanni Della Porta  1   2 , Patrizia Morbini  3   4 , Cristina Tassorelli  1   2 , Antonio Pisani  1   2
Affiliations

Neuropathological findings from COVID-19 patients with neurological symptoms argue against a direct brain invasion of SARS-CoV-2: A critical systematic review

Giuseppe Cosentino et al. Eur J Neurol. 2021 Nov.

Abstract

Background and purpose: 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 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.

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) 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.

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.

Keywords: COVID-19; SARS-CoV-2; brain; neurological symptoms; neuropathology.

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Conflict of interest statement

All authors declare no conflicts of interest regarding the content of this article.

Figures

FIGURE 1
FIGURE 1
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram.
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References

    1. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270‐273. - PMC - PubMed
    1. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of Covid‐19 in New York City. N Engl J Med. 2020;382:2372‐2374. - PMC - PubMed
    1. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus‐infected pneumonia in Wuhan, China. JAMA. 2020;323:1061‐1069. - PMC - PubMed
    1. Wolff D, Nee S, Hickey NS, Marschollek M. Risk factors for Covid‐19 severity and fatality: a structured literature review. Infection. 2021;49:15‐28. - PMC - PubMed
    1. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected With SARS‐CoV‐2 admitted to ICUs of the Lombardy region, Italy. JAMA. 2020;323:1574‐1581. - PMC - PubMed

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