COVID-19 with early neurological and cardiac thromboembolic phenomena—timeline of incidence and clinical features

  1. Uma Sundar
  2. Sanah Merchant
  3. Meera Shah
  4. Amita Mukhopadhyay
  5. Shaonak Kolte
  6. Pramod Darole
  7. Sharvari Mahajan
  8. Ashank Bansal
  9. Satish Gosavi
  10. Dnaneshwar Asole
  11. Niteen D Karnik
  12. Ajay Mahajan
  13. Anagha Joshi

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Abstract

Background

At our tertiary care public hospital, we saw COVID-19 presenting with thromboembolic phenomena, indicating a possible early thrombo-inflammatory pathology.

Objectives

We documented patients with cardiac and neurological thromboembolic phenomena as a primary presentation of COVID-19, and compared a subset of COVID associated strokes against COVID-19 patients without thrombotic manifestations.

Methods

We included all COVID-Stroke and COVID-ACS (COVID-19, with ischemic arterial stroke/Acute Coronary Syndrome presenting prior to/simultaneous with/within 72 hours of systemic/respiratory COVID manifestations) admitted from April to November 2020. In the nested case control analysis, we used unpaired T-test and chi-square test to study differences between COVID-Strokes (case group) and non-thrombotic COVID controls.

Results and Conclusions

We noted 68 strokes and 122 ACS associated with COVID-19. ACS peaked in May-June, while stroke admissions peaked later in September-October, possibly because severe strokes may have expired at home during the lockdown.

In the case-control analysis, cases (n=43; 12F:31M; mean age 51.5 years) had significantly higher D-Dimer values than controls (n=50; 9F:41M; mean age 51.6 years). Mortality was significantly higher in cases (51.2% vs. 26.0%; p = 0.018). We noted 7.5 times higher mortality in cases versus controls even among patients needing minimal oxygen support. Imaging in 37 patients showed both anterior and posterior circulation territories affected in seven, with almost half of Carotid territory strokes being large hemispherical strokes. Additionally, CT/MRI angiography in 28 strokes showed large vessel occlusions in 19 patients. Death in cases thus probably occurred before progression to intense respiratory support, due to severe central nervous system insult.

Binary logistic regression analysis showed respiratory support intensity to be the sole independent predictor of mortality among cases. Respiratory distress could have been due to COVID-19 lung infection or aspiration pneumonia resulting from obtunded sensorium. In controls, mortality was predicted by increasing age, female sex, and respiratory support intensity.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.15.21253619: (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

    Software and Algorithms
    SentencesResources
    We used Microsoft Excel (2010) to tabulate and clean the raw data, and to generate pivot tables and graphs.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)
    We imported the excel datasheet into IBM SPSS version 20.0 and performed univariate and multivariate analyses.
    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: We detected the following sentences addressing limitations in the study:
    Our sample size for the control group was small, and this limitation could have led to this finding. A major limitation of our study is the lack of documentation of clinical and subclinical pulmonary thromboembolic phenomena in the case and control groups. This was highly probable, given the thrombo-inflammatory milieu, and the concomitantly existing cerebral thrombosis. It is possible that this was more common in the case group and could have contributed to the mortality. We did not take pulmonary thromboembolism into account in our analysis, as complete data on CT pulmonary angiography was not available in many patients. In conclusion, our comparison of a thromboembolic cerebral presentation of COVID-19 with a clinically non-thromboembolic presentation of COVID-19, demonstrated higher D-Dimer levels, and a higher mortality in the absence of prominent respiratory compromise, in the former group. The higher mortality was possibly due to the severity of stroke and presence of proximal LVOs. We could not compare mortality in COVID-19 associated strokes with a cohort of non-COVID associated strokes in the same period, as our regular admissions were severely limited during the pandemic. A meta-analysis of stroke in COVID-19 has highlighted that the mean mortality rate among stroke patients with COVID-19 infection was 46.7% compared to only 8.7% among those without COVID-19 infection.(26)

    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.

  2. Version published to 10.1101/2021.03.15.21253619v1 on medRxiv