Central nervous system manifestations in COVID‐19 patients: A systematic review and meta‐analysis

  1. Shahrzad Nazari
  2. Amirhossein Azari Jafari
  3. Seyyedmohammadsadeq Mirmoeeni
  4. Saeid Sadeghian
  5. Mohammad Eghbal Heidari
  6. Siavash Sadeghian
  7. Farhad Assarzadegan
  8. Seyed Mahmoud Puormand
  9. Hamid Ebadi
  10. Davood Fathi
  11. Sahar Dalvand

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Abstract

Background

At the end of December 2019, a novel respiratory infection, initially reported in China, known as COVID‐19 initially reported in China, and later known as COVID‐19, led to a global pandemic. Despite many studies reporting respiratory infections as the primary manifestations of this illness, an increasing number of investigations have focused on the central nervous system (CNS) manifestations in COVID‐19. In this study, we aimed to evaluate the CNS presentations in COVID‐19 patients in an attempt to identify the common CNS features and provide a better overview to tackle this new pandemic.

Methods

In this systematic review and meta‐analysis, we searched PubMed, Web of Science, Ovid, EMBASE, Scopus, and Google Scholar. Included studies were publications that reported the CNS features between 1 January 2020 and 20 April 2020. The data of selected studies were screened and extracted independently by four reviewers. Extracted data analyzed by using STATA statistical software. The study protocol registered with PROSPERO (CRD42020184456).

Results

Of 2,353 retrieved studies, we selected 64 studies with 11,687 patients after screening. Most of the studies were conducted in China (58 studies). The most common CNS symptom of COVID‐19 was headache (8.69%, 95%CI: 6.76%–10.82%), dizziness (5.94%, 95%CI: 3.66%–8.22%), and impaired consciousness (1.90%, 95%CI: 1.0%–2.79%).

Conclusions

The growing number of studies has reported COVID‐19, CNS presentations as remarkable manifestations that happen. Hence, understanding the CNS characteristics of COVID‐19 can help us for better diagnosis and ultimately prevention of worse outcomes.

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  1. Version published to 10.1002/brb3.2025
  2. Version published to 10.1101/2020.07.21.20158691v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.07.21.20158691: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableData analysis and quality assessment: The desired data was recorded using an excel spreadsheet form that included the title, first author, year and month of publication, type of study, country, total sample size, the sample size of male and female, study design, demographic characteristics, exposure history, clinical manifestation, CNS symptoms, and any reported comorbidity.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We systematically searched Six databases including Google Scholar, Scopus, PubMed, Web of science, Ovid, and Embase for all published articles from January 1st, 2020 until April 20th, 2020 using the following Medical Subject Heading terms (MESH terms): (“Wuhan coronavirus” OR “Wuhan seafood market pneumonia virus” OR “COVID19 virus” OR “COVID-19 virus” OR “coronavirus disease 2019 virus” OR “SARS-CoV-2” OR “SARS2” OR “2019-nCoV” OR “2019 novel coronavirus” OR “2019-nCoV infection” OR “2019 novel coronavirus disease” OR “2019-nCoV disease” OR “coronavirus disease-19” OR “coronavirus disease 2019” OR “2019 novel coronavirus infection” OR “COVID19” OR “COVID-19” OR “severe acute respiratory syndrome coronavirus 2” OR “coronavirus*”) AND (“Manifestation, Neurologic” OR “Neurological Manifestations” OR “Neurologic Manifestation” OR “Neurological Manifestation” OR “Neurologic Symptom” OR “CNS” OR “brain” OR “neuro*” OR “headache” OR “dizziness” OR “ataxia” OR “epilepsy” OR “seizure” OR “migraine*” OR “CSF” OR “Cerebrospinal Fluids” OR “Fluid, Cerebrospinal” OR “Fluids, Cerebrospinal” OR “Cerebro Spinal Fluid” OR “Cerebro Spinal Fluids” OR “Fluid, Cerebro Spinal” OR “Fluids, Cerebro Spinal” OR “Spinal Fluid, Cerebro” OR “Spinal Fluids, Cerebro” OR “stroke” OR “vertigo” OR “consciousness” OR “Impaired consciousness” OR “coma” OR “cerebrovascular disease” OR “acute cerebrovascular disease” OR “encephalitis”) alone or in combination with OR and AND operators.
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    All analysis were performed using STATA statistical software, version 13 (StataCorp).
    STATA
    suggested: (Stata, RRID:SCR_012763)
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.21.20158691v1 on medRxiv