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

Adult Animals Antibodies, Neutralizing / immunology Antigens, Neoplasm / metabolism Biomarkers, Tumor / metabolism C-Reactive Protein / metabolism COVID-19 / metabolism Critical Care / statistics & numerical data Female HEK293 Cells Humans Kaplan-Meier Estimate Male Middle Aged Proteomics / methods RNA, Viral / blood SARS-CoV-2 / genetics Serum Amyloid P-Component / metabolism Spike Glycoprotein, Coronavirus / immunology Viral Load / immunology

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
07 06 2021
Historique:
received: 05 11 2020
accepted: 28 04 2021
entrez: 8 6 2021
pubmed: 9 6 2021
medline: 22 6 2021
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-021-23494-1 PMID: 34099652 PMC: PMC8184784
pubmed: 34099652
doi: 10.1038/s41467-021-23494-1
pii: 10.1038/s41467-021-23494-1
pmc: PMC8184784
doi:

Substances chimiques

Antibodies, Neutralizing 0
Antigens, Neoplasm 0
Biomarkers, Tumor 0
LGALS3BP protein, human 0
RNA, Viral 0
Serum Amyloid P-Component 0
Spike Glycoprotein, Coronavirus 0
spike protein, SARS-CoV-2 0
PTX3 protein 148591-49-5
C-Reactive Protein 9007-41-4

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3406

Subventions

Organisme : Department of Health
ID : CS-2016-16-011
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RM/17/3/33381
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/16/14/32397
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/16/3/32406
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/18/60/34181
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/18/2/34213
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V040162/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC/PC/15068
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001093
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R017751/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/19/58/34895
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/19/11/34633
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/17/48/32956
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/17/65/33481
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106292/Z/14/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/17/10/33219
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001093
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001093
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001093
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/1999001/11735
Pays : United Kingdom

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Auteurs

Clemens Gutmann (C)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0003-0675-8632

Kaloyan Takov (K)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0002-8642-6306

Sean A Burnap (SA)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0002-3408-8608

Bhawana Singh (B)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0002-5834-8320

Hashim Ali (H)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.

Konstantinos Theofilatos (K)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0001-6799-0553

Ella Reed (E)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.

Maria Hasman (M)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.

Adam 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.

Matthew 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.
ORCID: 0000-0001-6462-3889

Mark Jw 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.

Kevin 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.

Lukas E Schmidt (LE)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0001-7565-1455

Christian Cassel (C)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.

Marieke Rienks (M)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0002-0590-9518

Xiaoke Yin (X)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0002-5172-0935

Georg Auzinger (G)

King's College Hospital NHS Foundation Trust, London, UK.

Salvatore Napoli (S)

Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.

Salma F Mujib (SF)

Institute of Liver Studies, King's College Hospital, London, UK.

Francesca 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.

Barnaby Sanderson (B)

Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK.
ORCID: 0000-0002-9621-143X

Blair Merrick (B)

Clinical Infection and Diagnostics Research group, Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK.
ORCID: 0000-0002-6061-6064

Umar Niazi (U)

NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
ORCID: 0000-0001-7176-8883

Mansoor Saqi (M)

NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.

Konstantina Dimitrakopoulou (K)

NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.

Rafael Fernández-Leiro (R)

Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
ORCID: 0000-0002-7941-0357

Silke Braun (S)

Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
ORCID: 0000-0002-2558-1521

Romy Kronstein-Wiedemann (R)

Experimental Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, Technical University Dresden, Dresden, Germany.

Katie J Doores (KJ)

Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK.
ORCID: 0000-0002-5507-1725

Jonathan D 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.

Ajay M 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.

Stefan R 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.
ORCID: 0000-0002-5211-2536

Torsten 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.
ORCID: 0000-0001-9580-2193

Adrian C 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.
ORCID: 0000-0002-9495-5793

Mauro Giacca (M)

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London, UK.
ORCID: 0000-0003-2927-7225

Manu 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.
ORCID: 0000-0002-5338-2538

Manuel 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.
ORCID: 0000-0002-0597-829X

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › SARS-CoV-2 RNAemia and proteomic trajectories...
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