Clearing the Fog: a Systematic Review on Cognitive Dysfunction in COVID-19

  1. Nicole Butardo
  2. Mikaela Frances Coronel
  3. Alanna Marie Dino
  4. Tiffany Ritz Mendoza
  5. Oliver Kyle Sto. Domingo
  6. Zypher Jude Regencia
  7. Jacqueline Dominguez
  8. Emmanuel Baja
  9. Antonio Ligsay

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Abstract

[Objective] The systematic review aims to examine the association between COVID-19 and cognitive dysfunction, including the link between the severity of COVID-19 and the occurrence of cognitive impairment and the potential pathophysiological mechanisms related to brain fog among COVID-19 patients. [Methods] PubMed, Oxford University Press, ProQuest Health and Medical Complete, ScienceDirect, Ovid, HERDIN, Google Scholar, and Cochrane Library databases were accessed to retrieve literature using the PRISMA guidelines. [Results] After critical appraisal, 13 full journal articles were included in the study. The studies showed the most frequent cognitive impairment are attention, memory, and executive function in COVID-19 patients. Compared with healthy controls in three out of four studies, cognitive impairment was only evident in COVID-19 patients. Furthermore, two studies showed no correlation between brain fog and depression, and five studies showed a link between the severity of COVID-19 infection and cognitive impairment. Cases ranging from mild to severe illness presented manifestations of brain fog. However, a disparity in the evidence of the pathophysiology of COVID-19 and cognitive dysfunction exists, prompting the need to investigate further. Additionally, recent studies provide insufficient evidence for direct central nervous system invasion, and there are emerging studies that contrast the presumed pathogenesis of neurological complications from neuroinflammation. [Conclusion] There is an association between COVID-19 and cognitive dysfunction. Manifestation of cognitive dysfunction is present regardless of illness severity. Moreover, there are existing pathophysiological mechanisms of the Coronavirus that lead to cognitive dysfunction in COVID-19 patients; however, additional studies are required to substantiate such mechanisms further. [PROSPERO registration number] CRD42022325669.

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  1. Version published to 10.56899/151.6a.01
  2. ScreenIT

    SciScore for 10.1101/2022.05.24.22275552: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    , ProQuest Health and Medical Complete, ScienceDirect, Ovid, HERDIN, Google Scholar, and Cochrane Library.
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)

    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: We detected the following sentences addressing limitations in the study:
    Another limitation is the possibility that some relevant studies were not taken into account because they have been published in languages other than English (e.g., Chinese). We also did not have access to some other databases that may store some articles on COVID-19 and cognitive dysfunctions. And lastly, there could be some other studies on this theme in the literature that skipped our attention and analyses. However, a comprehensive search strategy that covers a broad range of evidence was implemented. This systematic review gathered evidence that could provide clarity on the association between brain fog and COVID-19 infection. The information acquired in this study may help re-evaluate the impact of the virus. Furthermore, the use of the data gleaned from this analysis may assist in earlier treatment, allowing physicians and clinicians to manage the neurological manifestation effectively. Additionally, this will aid in the development of various therapeutic strategies to support COVID-19 patients in recovering from impaired cognitive capacity. Finally, the analysis of such data could provide an insight into the challenges that this virus could cause people in their prime years, particularly those in the workforce.

    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.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    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.

  3. Version published to 10.1101/2022.05.24.22275552v1 on medRxiv