Functional and microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19

  1. Lucas Scardua Silva
  2. Rafael Batista Joao
  3. Mateus Henrique Nogueira
  4. Italo Karmann Aventurato
  5. Brunno Machado de Campos
  6. Mariana Rabelo de Brito
  7. Marina Koutsodontis Machado Alvim
  8. Guilherme Vieira Nunes Ludwig
  9. Cristiane Rocha
  10. Thierry Kaue Alves Silva Souza
  11. Beatriz Amorim da Costa
  12. Maria Julia Mendes
  13. Takeshi Waku
  14. Vinicius de Oliveira Boldrini
  15. Natália Silva Brunetti
  16. Sophia Nora Baptista
  17. Gabriel da Silva Schmitt
  18. Jhulia Gabriela Duarte de Sousa
  19. Tânia Aparecida Marchiori de Oliveira Cardoso
  20. André Schwambach Vieira
  21. Leonilda Maria Barbosa Santos
  22. Alessandro dos Santos Farias
  23. Fernando Cendes
  24. Clarissa Lin Yasuda

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Abstract

Although post-acute cognitive dysfunction and neuroimaging abnormalities have been reported after hospital discharge in patients recovered from COVID-19, little is known about persistent, long-term alterations in patients who did not require hospitalization. Therefore, we conducted a cross-sectional study of 87 consecutive, non-hospitalized recovered individuals, with a median of 54 days after the laboratory confirmation of COVID-19. We performed structured interviews, neurological examination, and 3T-MRI scans. The MRI study included white matter investigation with diffusion tensor images (DTI) and seed-based resting-state functional MRI (fMRI) connectivity analyses of the default mode network (DMN). In addition, we used validated instruments to examine fatigue, symptoms of anxiety and depression, somnolence, language, memory, and cognitive flexibility.

Individuals self-reported a high frequency of headaches (40%) and memory difficulties (33%). The quantitative analyses confirmed symptoms of fatigue (68% of participants), excessive somnolence (35%), symptoms of anxiety (29%), impaired cognitive flexibility (40%) and language dysfunction (33%). In addition, we observed a correlation between DTI fractional anisotropy (FA) and abnormal attention and cognitive flexibility measured by the Trail Making Test part B. The resting-state fMRI study of the DMN showed an association between higher connectivity of the posterior cingulate cortex (PCC) and higher levels of fatigue and somnolence. While greater connectivity of the PCC with bilateral angular gyri was associated with higher fatigue levels, the elevated levels of somnolence correlated with higher connectivity between the PCC and both the left thalamus and putamen.

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  1. Version published to 10.1101/2021.03.20.21253414v2 on medRxiv
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    SciScore for 10.1101/2021.03.20.21253414: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Research Ethics Committee of the University of Campinas (Certificate of Ethical Appreciation Presentation - CAAE 31556920.0.0000.5404), and all subjects signed a consent form to participate.
    Consent: This study was approved by the Research Ethics Committee of the University of Campinas (Certificate of Ethical Appreciation Presentation - CAAE 31556920.0.0000.5404), and all subjects signed a consent form to participate.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    We successively recruited the first 87 responders (who did not require hospitalization and presented a confirmed diagnosis of COVID-19 (by a polymerase chain reaction [PCR] test or confirmed presence of IgM or IgG antibodies) to visit our center and perform the four steps of the complete protocol: a personal structured interview and neurological examination (performed by certified neurologists), 3T MRI acquisition, neuropsychological testing, and blood sample collection at our University Hospital (University of Campinas, Campinas, Brazil).
    IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses: Clinical data were analyzed with SPSS 22.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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.

  3. Version published to 10.1101/2021.03.20.21253414v1 on medRxiv