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

Autor: Gutmann C; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Takov K; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Burnap SA; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Singh B; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Ali H; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Theofilatos K; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Reed E; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Hasman M; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Nabeebaccus A; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.; King's College Hospital NHS Foundation Trust, London, UK., Fish M; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK.; Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK., McPhail MJ; King's College Hospital NHS Foundation Trust, London, UK.; Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.; Institute of Liver Studies, King's College Hospital, London, UK., O'Gallagher K; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.; King's College Hospital NHS Foundation Trust, London, UK., Schmidt LE; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Cassel C; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Rienks M; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Yin X; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Auzinger G; King's College Hospital NHS Foundation Trust, London, UK., Napoli S; Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK., Mujib SF; Institute of Liver Studies, King's College Hospital, London, UK., Trovato F; King's College Hospital NHS Foundation Trust, London, UK.; Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.; Institute of Liver Studies, King's College Hospital, London, UK., Sanderson B; Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK., Merrick B; Clinical Infection and Diagnostics Research group, Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK., Niazi U; NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK., Saqi M; NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK., Dimitrakopoulou K; NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK., Fernández-Leiro R; Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Braun S; Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany., Kronstein-Wiedemann R; Experimental Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, Technical University Dresden, Dresden, Germany., Doores KJ; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK., Edgeworth JD; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK.; Clinical Infection and Diagnostics Research group, Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK., Shah AM; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.; King's College Hospital NHS Foundation Trust, London, UK., Bornstein SR; Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.; Department of Diabetes, School of Life Course Science and Medicine, King's College London, London, UK., Tonn T; Experimental Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, Technical University Dresden, Dresden, Germany.; Institute for Transfusion Medicine, German Red Cross Blood Donation Service North East, Dresden, Germany., Hayday AC; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK.; The Francis Crick Institute, London, UK., Giacca M; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK., Shankar-Hari M; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK. manu.shankar-hari@kcl.ac.uk.; Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK. manu.shankar-hari@kcl.ac.uk., Mayr M; King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK. manuel.mayr@kcl.ac.uk.; Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. manuel.mayr@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jun 07; Vol. 12 (1), pp. 3406. Date of Electronic Publication: 2021 Jun 07.
DOI: 10.1038/s41467-021-23494-1
Abstrakt: 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.
Databáze: MEDLINE
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