Thromboembolic risk in hospitalised and non-hospitalised Covid-19 patients: A self-controlled case series analysis of a nation-wide cohort

  1. Frederick K Ho
  2. Kenneth KS Man
  3. Mark Toshner
  4. Colin Church
  5. Carlos Celis-Morales
  6. Ian CK Wong
  7. Colin Berry
  8. Naveed Sattar
  9. Jill P Pell

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Abstract

Objective

An unexpectedly large number of people infected with Covid-19 had experienced a thrombotic event. This study aims to assess the associations between Covid-19 infection and thromboembolism including myocardial infarction (MI), ischaemic stroke, deep-vein thrombosis (DVT), and pulmonary embolism (PE).

Patients and Methods

A self-controlled case-series study was conducted covering the whole of Scotland’s general population. The study population comprised individuals with confirmed (positive test) Covid-19 and at least one thromboembolic event between March 2018 and October 2020. Their incidence rates during the risk interval (5 days before to 56 days after the positive test) and the control interval (the remaining periods) were compared intra-personally.

Results

Across Scotland, 1,449 individuals tested positive for Covid-19 and experienced a thromboembolic event. The risk of thromboembolism was significantly elevated over the whole risk period but highest in the 7 days following the positive test (IRR 12.01, 95% CI 9.91-14.56) in all included individuals. The association was also present in individuals not originally hospitalised for Covid-19 (IRR 4.07, 95% CI 2.83-5.85). Risk of MI, stroke, PE and DVT were all significantly higher in the week following a positive test. The risk of PE and DVT was particularly high and remained significantly elevated even 56 days following the test.

Conclusion

Confirmed Covid-19 infection was associated with early elevations in risk with MI, ischaemic stroke, and substantially stronger and prolonged elevations with DVT and PE both in hospital and community settings. Clinicians should consider thromboembolism, especially PE, among people with Covid-19 in the community.

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  1. Version published to 10.1101/2021.02.02.21251043v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.02.02.21251043: (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 variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    However, the findings of this study are still subject to the following limitations. To ensure internal validity, this study opted for the SCCS method, which only included patients with at least one thromboembolism during the study period. However, this may limit the generalisability of the findings to people with lower risk of these events. It should be noted that, if the elevated risk of PE is truly causal, the estimates that we provided could be an underestimate. The IRR for the latest categories in the risk interval was still significantly greater than one, suggesting a long tail of risk elevation and thus some of the pre- and post-infection control interval could be misspecified. Patients with no or mild symptoms from Covid-19 infection are less likely to have been tested, especially at the beginning of the pandemic when testing capacity was lower. The increased risk of thromboembolism demonstrated in the days prior to confirmed infection is likely to reflect the time lag between actual date of infection and our proxy measure of it; date of specimen collection. Reverse causation is possible in some patients; for example, nosocomial infection of patients hospitalised for thromboembolic events. However, the lack of an association with elective surgery suggests that any reverse causation is unlikely to fully explain our findings. The lowered risk in extended pre-test interval for outcomes except MI also does not support strong reverse causation. It is highly likely that ther...

    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

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  3. Version published to 10.1101/2021.02.02.21251043v1 on medRxiv