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      A systematic review of neurological symptoms and complications of COVID-19

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          Abstract

          Objective

          To study the frequency of neurological symptoms and complications in COVID-19 patients in a systematic review of the literature.

          Methods

          Relevant studies were identified through electronic explorations of PubMed, medRxiv, and bioRxiv. Besides, three Chinese databases were searched. A snowballing method searching the bibliographies of the retrieved references was applied to identify potentially relevant articles. Articles published within 1 year prior to April 20th, 2020, were screened with no language restriction imposed. Databases were searched for terms related to SARS-CoV-2/COVID-19 and neurological manifestations, using a pre-established protocol registered on the International Prospective Register of Systematic Reviews database (ID: CRD42020187994).

          Results

          A total of 2441 articles were screened for relevant content, of which 92 full-text publications were included in the analyses of neurological manifestations of COVID-19. Headache, dizziness, taste and smell dysfunctions, and impaired consciousness were the most frequently described neurological symptoms, the latter more often among patients with a severe or critical disease course. To date, only smaller cohort studies or single cases have reported cerebrovascular events, seizures, meningoencephalitis, and immune-mediated neurological diseases, not suitable for quantitative analysis.

          Conclusion

          The most frequent neurological symptoms reported in association with COVID-19 are non-specific for the infection with SARS-CoV-2. Although SARS-CoV-2 may have the potential to gain direct access to the nervous system, so far, SARS-CoV-2 was detected in the cerebrospinal fluid in two cases only. Standardized international registries are needed to clarify the clinical relevance of the neuropathogenicity of SARS-CoV-2 and to elucidate a possible impact of SARS-CoV-2 infection on common neurological disease, such as Alzheimer’s, Parkinson’s disease or multiple sclerosis.

          Electronic supplementary material

          The online version of this article (10.1007/s00415-020-10067-3) contains supplementary material, which is available to authorized users.

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          Most cited references52

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Na Zhu, Dingyu Zhang, Wenling Wang … (2020)
          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)
            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
            Article 0 comments Cited 9619 times – based on 0 reviews     Review now
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              Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

              Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett … (2020)
              Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260
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                Author and article information

                Contributors
                Finja Schweitzer: finja.schweitzer@uk-koeln.de
                Clemens Warnke:
                ORCID: http://orcid.org/0000-0002-3510-9255
                clemens.warnke@uk-koeln.de
                Journal
                Journal ID (nlm-ta): J Neurol
                Journal ID (iso-abbrev): J. Neurol
                Title: Journal of Neurology
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0340-5354
                ISSN (Electronic): 1432-1459
                Publication date (Electronic): 20 July 2020
                Publication date PMC-release: 20 July 2020
                Pages: 1-11
                Affiliations
                [1 ]Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
                [2 ]GRID grid.6190.e, ISNI 0000 0000 8580 3777, Department of Neurology, Faculty of Medicine and University Hospital Cologne, , University of Cologne, ; Kerpener Street 62, 50937 Cologne, Germany
                [3 ]GRID grid.8385.6, ISNI 0000 0001 2297 375X, Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), , Research Centre Jülich, ; Leo-Brandt-Strasse, Jülich, 52425 Germany
                Author information
                http://orcid.org/0000-0002-3510-9255
                Article
                Publisher ID: 10067
                DOI: 10.1007/s00415-020-10067-3
                PMC ID: 7370630
                PubMed ID: 32691236
                SO-VID: b80588bb-598d-4656-9a28-80c99b9261b6
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 14 June 2020
                Date revision received : 7 July 2020
                Date accepted : 9 July 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Neurology
                Keywords: sars-cov-2,covid-19,neuro-covid,nervous system
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: sars-cov-2, covid-19, neuro-covid, nervous system

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