Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study

  1. Kamen A Tsvetanov
  2. Lennart R B Spindler
  3. Emmanuel A Stamatakis
  4. Virginia FJ Newcombe
  5. Victoria C Lupson
  6. Doris A Chatfield
  7. Anne E Manktelow
  8. Joanne G Outtrim
  9. Anne Elmer
  10. Nathalie Kingston
  11. John R Bradley
  12. Edward T Bullmore
  13. James B Rowe
  14. David K Menon
  15. The Cambridge NeuroCOVID Group
  16. The NIHR COVID-19 BioResource
  17. The Cambridge NIHR Clinical Research Facility
  18. The CITIID-NIHR BioResource COVID-19 Collaboration

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Abstract

Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. Here we assess cerebrovascular health in 45 hospitalised patients using the resting state fluctuation amplitudes (RSFA) from functional magnetic resonance imaging, in relation to disease severity and in contrast with 42 controls. Widespread changes in frontoparietal RSFA were related to the severity of the acute COVID-19 episode, as indexed by COVID-19 WHO Progression Scale, inflammatory and coagulatory biomarkers. This relationship was not explained by chronic cardiorespiratory dysfunction, age, or sex. Exploratory analysis suggests that the level of cerebrovascular dysfunction is associated with cognitive, mental, and physical health at follow-up. The principal findings were consistent across univariate and multivariate approaches. The results indicate chronic cerebrovascular impairment following severe acute COVID-19, with the potential for long-term consequences on cognitive function and mental wellbeing.

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    SciScore for 10.1101/2022.02.01.22270235: (What is this?)

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    Table 1: Rigor

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    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Pulse oximetry, monitored via GE Carescape V100 Dinamap Vital Signs Monitor (GE Healthcare Systems, Chicago, Illinois, USA), was used to determine the heart rate and arterial oxygen saturation before and following a 6-minute walk test (Bois et al., 2012; Crapo et al., 2012; PL et al., 2003). 2.4.
    GE Healthcare Systems
    suggested: None
    Significant effects of interest were identified with nonparametric testing using 10.000 permutations using commonality analysis implementation in Matlab (Wu et al., 2021). 2.5.3.
    Matlab
    suggested: (MATLAB, RRID:SCR_001622)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has several limitations. We are limited by the relatively small sample size, and by the absence of longitudinal imaging data. We also do not draw any causal inferences from the associations we observe. However, the demonstration of functional microvascular abnormalities following COVID-19 is important to understand the potential mechanisms of persistent cognitive and mental health problems. The association of microvascular abnormalities with late outcomes of relevance to patients, and the fact that they represent an easily accessible biomarker, suggest both a potential therapeutic target and/or a biomarker of treatment effect in interventional studies. It remains to be shown whether the localisation of RSFA abnormalities to regions rich in 5HT-1b receptors is a consequence of overactivity of these receptors (resulting in low cerebral blood flow), underactivity or loss of these receptors (resulting in vasoparalysis and/or inflammation), or a manifestation of flow-metabolism mismatching with inadequate substrate and oxygen delivery. This is relevant as potential therapeutic agents that are available to modulate both 5HT-1b function (Barnes et al 2021) and inflammatory response (Zhang et al., 2020) (Group et al., 2021b; Zhang et al., 2020). In summary, we demonstrate that the severity of acute COVID-19 predicts cerebrovascular impairment six months later. The cerebrovascular abnormality was associated with worse cognitive function, mental health, functional recovery, a...

    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.

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

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  2. Version published to 10.1101/2022.02.01.22270235v1 on medRxiv
  3. Version published to 10.1016/j.nicl.2022.103253