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Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence

Author

Listed:
  • Jack S. Gisby

    (Imperial College London)

  • Norzawani B. Buang

    (Imperial College London)

  • Artemis Papadaki

    (Imperial College London)

  • Candice L. Clarke

    (Imperial College London
    Imperial College Healthcare NHS Trust)

  • Talat H. Malik

    (Imperial College London)

  • Nicholas Medjeral-Thomas

    (Imperial College London
    Imperial College Healthcare NHS Trust)

  • Damiola Pinheiro

    (Imperial College London)

  • Paige M. Mortimer

    (Imperial College London)

  • Shanice Lewis

    (Imperial College London)

  • Eleanor Sandhu

    (Imperial College London
    Imperial College Healthcare NHS Trust)

  • Stephen P. McAdoo

    (Imperial College London
    Imperial College Healthcare NHS Trust)

  • Maria F. Prendecki

    (Imperial College London
    Imperial College Healthcare NHS Trust)

  • Michelle Willicombe

    (Imperial College London
    Imperial College Healthcare NHS Trust)

  • Matthew C. Pickering

    (Imperial College London)

  • Marina Botto

    (Imperial College London)

  • David C. Thomas

    (Imperial College London
    Imperial College Healthcare NHS Trust)

  • James E. Peters

    (Imperial College London)

Abstract

Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.

Suggested Citation

  • Jack S. Gisby & Norzawani B. Buang & Artemis Papadaki & Candice L. Clarke & Talat H. Malik & Nicholas Medjeral-Thomas & Damiola Pinheiro & Paige M. Mortimer & Shanice Lewis & Eleanor Sandhu & Stephen , 2022. "Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35454-4
    DOI: 10.1038/s41467-022-35454-4
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    References listed on IDEAS

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    Cited by:

    1. Erik Duijvelaar & Jack Gisby & James E. Peters & Harm Jan Bogaard & Jurjan Aman, 2024. "Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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