Association of cerebral venous thrombosis with recent COVID-19 vaccination: case-crossover study using ascertainment through neuroimaging in Scotland

  1. Paul M. McKeigue
  2. Raj Burgul
  3. Jen Bishop
  4. Chris Robertson
  5. Jim McMenamin
  6. Maureen O’Leary
  7. David A. McAllister
  8. Helen M. Colhoun

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Abstract

Background

To investigate the association of primary acute cerebral venous thrombosis (CVT) with COVID-19 vaccination through complete ascertainment of all diagnosed CVT in the population of Scotland.

Methods

Case-crossover study comparing cases of CVT recently exposed to vaccination (1–14 days after vaccination) with cases less recently exposed. Cases in Scotland from 1 December 2020 were ascertained through neuroimaging studies up to 17 May 2021 and diagnostic coding of hospital discharges up to 28 April 2021, linked to national vaccination records. The main outcome measure was primary acute CVT.

Results

Of 50 primary acute CVT cases, 29 were ascertained only from neuroimaging studies, 2 were ascertained only from hospital discharges, and 19 were ascertained from both sources. Of these 50 cases, 14 had received the Astra-Zeneca ChAdOx1 vaccine and 3 the Pfizer BNT162b2 vaccine. The incidence of CVT per million doses in the first 14 days after vaccination was 2.2 (95% credible interval 0.9 to 4.1) for ChAdOx1 and 1 (95% credible interval 0.1 to 2.9) for BNT162b2. The rate ratio for CVT associated with exposure to ChAdOx1 in the first 14 days compared with exposure 15-84 days after vaccination was 3.2 (95% credible interval 1.1 to 9.5).

Conclusions

These findings support a causal association between CVT and the AstraZeneca vaccine. The absolute risk of post-vaccination CVT in this population-wide study in Scotland was lower than has been reported for populations in Scandinavia and Germany; the explanation for this is not clear.

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  1. Version published to 10.1186/s12879-021-06960-5
  2. ScreenIT

    SciScore for 10.1101/2021.08.23.21261779: (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.
    RandomizationA second doctor re-scored all scans that had been coded non-negative and a random sample of negative scans, with the scoring of the first reviewer masked.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and limitations of this study: A strength of this study is the complete ascertainment of cases in the population, not reliant on adverse event reporting or diagnostic coding of hospital discharge records. Manual review of scan reports, which typically included a summary of the clinical history allowed some CVT cases to be recoded as secondary to a local lesion such as a tumour, allowed some to be recoded as chronic rather than acute CVT, and allowed the date of onset to be determined accurately. Accurate assignment of date of onset is required for the case-crossover analysis to be valid. The case-crossover design eliminates confounding by time-invariant factors, which may be strong where vaccine allocation is based on pre-existing risk conditions that were used to allocate priority for vaccination. This has allowed us to show that for the Astra Zeneca there is evidence of a causal association of CVT with vaccine exposure. Note that our analysis assumes an ignorance prior; it ignores any prior evidence of association. Limitations of our study are that we do not have access to data on platelet counts, D-dimer or platelet factor 4 antibody levels, allowing enumeration of the number of CVT events that are part of the formally defined VITT / TTS syndrome as meeting associated haematological criteria. We note that the Brighton Collaborative however acknowledges that the TTS syndrome definition may be too restrictive by excluding isolated thrombotic events that are causall...

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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

    About SciScore

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  3. Version published to 10.1101/2021.08.23.21261779 on medRxiv