Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID‐19

  1. Shirjel R. Alam
  2. Sudhir Vinayak
  3. Adeel Shah
  4. Gemina Doolub
  5. Redemptar Kimeu
  6. Kevin P. Horn
  7. Stephen R. Bowen
  8. Mohamed Jeilan
  9. Kuan Ken Lee
  10. Sylvia Gachoka
  11. Felix Riunga
  12. Rodney D. Adam
  13. Hubert Vesselle
  14. Nikhil Joshi
  15. Mariah Obino
  16. Khalid Makhdomi
  17. Kevin Ombati
  18. Edward Nganga
  19. Samuel Gitau
  20. Michael H. Chung
  21. Anoop S. V. Shah

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Abstract

Acute COVID‐19–related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID‐19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis.

Methods and Results

Consecutive patients presenting with acute COVID‐19 were prospectively recruited during hospital admission in this cross‐sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2‐deoxy‐2‐[fluorine‐18]fluoro‐D‐glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance–defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0–55.3] versus 3.5 ng/L [IQR: 2.5–5.5]; P =0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4–8.3] versus 3.5 ng/L [IQR: 2.8–7.2]; P =0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%–31%) and 11% (IQR: 7%–18%), respectively. Neither were associated with the presence of myocarditis.

Conclusions

Myocarditis was present in a third patients with acute COVID‐19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process.

Registration

URL: https://www.isrctn.com ; Unique identifier: ISRCTN12154994.

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  1. Version published to 10.1161/jaha.122.026399
  2. ScreenIT

    SciScore for 10.1101/2022.03.21.22272698: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study complies with the Declaration of Helsinki with study approval from the Aga Khan University Nairobi Institutional Ethics Review Committee (Reference: 2020/IERC-74 (v2).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot 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:
    Our study has some limitations. Firstly, although achieving comprehensive phenotyping this was an observational study in a small COVID-19 population. Almost half of the patients received either dexamethasone or remdesevir which may have supressed the inflammatory response and underestimated myocardial inflammation. Scanning, however, was performed early in the clinical course. Secondly, our assessment of vasculitis was based on 18F-FDG-PET/CT uptake in the large vessels. Vascular inflammation in the smaller vessels, due to limited spatial resolution, may be undetected. However, if vascular inflammation was secondary to a systemic cytokine storm or immune response, it would have been expected that this would have been reflected in the aorta and the medium sized carotids. Thirdly, we excluded patients with severe COVID-19 infection who were unable to tolerate imaging limiting the generalizability of our findings in this population. Finally, we did not perform cardiac biopsy. Although this is the gold standard for the diagnosis of myocarditis, we performed deep phenotyping using three different imaging modalities. The combination of myocardial inflammatory cell identifaction by 18F-FDG-PET, and myocarditis detection by CMR (using the strictest criteria to identify oedema), make our findings robust. In conclusions, for the first time in acute COVID-19 infection and with the use of multi-modality imaging we make the following observations. Myocarditis was present in one in three p...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    ISRCTN12154994NANA

    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.

    About SciScore

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  3. Version published to 10.1101/2022.03.21.22272698v1 on medRxiv