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

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’Gallagher, Lukas E. Schmidt, Christian Cassel, Marieke Rienks, Xiaoke Yin, Georg Auzinger, Salvatore Napoli, Salma F. Mujib, Francesca Trovato, Barnaby Sanderson, Blair Merrick, Umar Niazi, Mansoor Saqi, Konstantina Dimitrakopoulou, Rafael Fernández-Leiro, Silke Braun, Romy Kronstein-Wiedemann, Katie J. Doores, Jonathan D. Edgeworth, Ajay M. Shah, Stefan R. Bornstein, Torsten Tonn, Adrian C. Hayday, Mauro Giacca, Manu Shankar-Hari () and Manuel Mayr ()
Additional contact information
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
Matthew Fish: Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London
Mark JW. McPhail: King’s College Hospital NHS Foundation Trust
Kevin O’Gallagher: King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences
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
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
Ajay M. Shah: King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences
Stefan R. Bornstein: Technical University Dresden
Torsten Tonn: Technical University Dresden
Adrian C. Hayday: Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London
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
Manuel Mayr: King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23494-1

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