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SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care

Author

Listed:
  • Clemens Gutmann

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Kaloyan Takov

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Sean A. Burnap

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Bhawana Singh

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Hashim Ali

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Konstantinos Theofilatos

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Ella Reed

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Maria Hasman

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Adam Nabeebaccus

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences
    King’s College Hospital NHS Foundation Trust)

  • Matthew Fish

    (Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London
    Department of Intensive Care Medicine, Guy’s and St Thomas’ NHS Foundation Trust)

  • Mark JW. McPhail

    (King’s College Hospital NHS Foundation Trust
    Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London
    Institute of Liver Studies, King’s College Hospital)

  • Kevin O’Gallagher

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences
    King’s College Hospital NHS Foundation Trust)

  • Lukas E. Schmidt

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Christian Cassel

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Marieke Rienks

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Xiaoke Yin

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Georg Auzinger

    (King’s College Hospital NHS Foundation Trust)

  • Salvatore Napoli

    (Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London)

  • Salma F. Mujib

    (Institute of Liver Studies, King’s College Hospital)

  • Francesca Trovato

    (King’s College Hospital NHS Foundation Trust
    Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London
    Institute of Liver Studies, King’s College Hospital)

  • Barnaby Sanderson

    (Department of Intensive Care Medicine, Guy’s and St Thomas’ NHS Foundation Trust)

  • Blair Merrick

    (Clinical Infection and Diagnostics Research group, Department of Infection, Guy’s and St Thomas’ NHS Foundation Trust)

  • Umar Niazi

    (NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London)

  • Mansoor Saqi

    (NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London)

  • Konstantina Dimitrakopoulou

    (NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London)

  • Rafael Fernández-Leiro

    (Structural Biology Programme, Spanish National Cancer Research Centre (CNIO))

  • Silke Braun

    (Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden)

  • Romy Kronstein-Wiedemann

    (Technical University Dresden)

  • Katie J. Doores

    (Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London)

  • Jonathan D. Edgeworth

    (Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London
    Clinical Infection and Diagnostics Research group, Department of Infection, Guy’s and St Thomas’ NHS Foundation Trust)

  • Ajay M. Shah

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences
    King’s College Hospital NHS Foundation Trust)

  • Stefan R. Bornstein

    (Technical University Dresden
    Department of Diabetes, School of Life Course Science and Medicine, King’s College London)

  • Torsten Tonn

    (Technical University Dresden
    Institute for Transfusion Medicine, German Red Cross Blood Donation Service North East)

  • Adrian C. Hayday

    (Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London
    The Francis Crick Institute)

  • Mauro Giacca

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences)

  • Manu Shankar-Hari

    (Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London
    Department of Intensive Care Medicine, Guy’s and St Thomas’ NHS Foundation Trust)

  • Manuel Mayr

    (King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences
    Technical University Dresden)

Abstract

Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified ‘Age, RNAemia’ and ‘Age, PTX3’ as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro.

Suggested Citation

  • Clemens Gutmann & Kaloyan Takov & Sean A. Burnap & Bhawana Singh & Hashim Ali & Konstantinos Theofilatos & Ella Reed & Maria Hasman & Adam Nabeebaccus & Matthew Fish & Mark JW. McPhail & Kevin O’Galla, 2021. "SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23494-1
    DOI: 10.1038/s41467-021-23494-1
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    Cited by:

    1. 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.
    2. Yanhua Li & Shijie Qin & Lei Dong & Shitong Qiao & Xiao Wang & Dongshan Yu & Pengyue Gao & Yali Hou & Shouzhen Quan & Ying Li & Fengyan Fan & Xin Zhao & Yueyun Ma & George Fu Gao, 2024. "Long-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Haris Babačić & Wanda Christ & José Eduardo Araújo & Georgios Mermelekas & Nidhi Sharma & Janne Tynell & Marina García & Renata Varnaite & Hilmir Asgeirsson & Hedvig Glans & Janne Lehtiö & Sara Gredma, 2023. "Comprehensive proteomics and meta-analysis of COVID-19 host response," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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