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Article
Manuel Mayr, Clemens Gutmann, Kaloyan Takov, Sean Burnap, Bhawana Singh, Konstantinos Theofilatos, Ella Reed, Maria Hasman, Adam Nabeebaccus, Matthew Fish, Mark McPhail, Kevin O'Gallagher, Lukas Schmidt, Christian Cassel, Marieke Rienks, Xiaoke Yin, Georg Auzinger, Salvatore Napoli, Salma Mujib, Francesca Trovato, Barnaby Sanderson, Blair Merrick, Umar Niazi, Mansoor Saqi, Konstantina Dimitrakopoulou, Silke Braun, Romy Kronstein-Wiedemann, Katie Doores, Jonathan Edgeworth, Ajay Shah, Stefan Bornstein, Torsten Tonn, Adrian Hayday, Manu Shankar-Hari
Manuel Mayr
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0597-829X
Clemens Gutmann
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
ORCiD: https://orcid.org/0000-0003-0675-8632
Kaloyan Takov
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
ORCiD: https://orcid.org/0000-0002-8642-6306
Sean Burnap
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
ORCiD: https://orcid.org/0000-0002-3408-8608
Bhawana Singh
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Konstantinos Theofilatos
King's College
ORCiD: https://orcid.org/0000-0001-6799-0553
Ella Reed
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Maria Hasman
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Adam Nabeebaccus
King's College Hospital NHS Foundation Trust, London
Matthew Fish
King's College London
ORCiD: https://orcid.org/0000-0001-6462-3889
Mark McPhail
Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London
Kevin O'Gallagher
King's College Hospital NHS Foundation Trust, London
Lukas Schmidt
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Christian Cassel
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Marieke Rienks
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
ORCiD: https://orcid.org/0000-0002-0590-9518
Xiaoke Yin
King's College London
ORCiD: https://orcid.org/0000-0002-5172-0935
Georg Auzinger
King's College Hospital NHS Foundation Trust, London
Salvatore Napoli
Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London
Salma Mujib
Institute of Liver Studies, King’s College Hospital, London
Francesca Trovato
King's College Hospital NHS Foundation Trust, London
Barnaby Sanderson
Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London
ORCiD: https://orcid.org/0000-0002-9621-143X
Blair Merrick
Guy's and St Thomas' NHS Foundation Trust
ORCiD: https://orcid.org/0000-0002-6061-6064
Umar Niazi
King's College London
ORCiD: https://orcid.org/0000-0001-7176-8883
Mansoor Saqi
NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust
Konstantina Dimitrakopoulou
NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London
Silke Braun
Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden
Romy Kronstein-Wiedemann
Medical Faculty Carl Gustav Carus, Technische Universität Dresden
Katie Doores
King's College London
ORCiD: https://orcid.org/0000-0002-5507-1725
Jonathan Edgeworth
5th Floor North Wing, St Thomas' Hospital, London, UK
Ajay Shah
King's College London
Stefan Bornstein
Medical Faculty Carl Gustav Carus at the Technical University of Dresden
Torsten Tonn
Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
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 was associated with higher 28-day ICU mortality (hazard ratio HR, 1.84 95% CI, 1.22–2.77 adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.
This is a preprint. It has not completed peer review.
Article
Manuel Mayr, Clemens Gutmann, Kaloyan Takov, Sean Burnap, Bhawana Singh, Konstantinos Theofilatos, Ella Reed, Maria Hasman, Adam Nabeebaccus, Matthew Fish, Mark McPhail, Kevin O'Gallagher, Lukas Schmidt, Christian Cassel, Marieke Rienks, Xiaoke Yin, Georg Auzinger, Salvatore Napoli, Salma Mujib, Francesca Trovato, Barnaby Sanderson, Blair Merrick, Umar Niazi, Mansoor Saqi, Konstantina Dimitrakopoulou, Silke Braun, Romy Kronstein-Wiedemann, Katie Doores, Jonathan Edgeworth, Ajay Shah, Stefan Bornstein, Torsten Tonn, Adrian Hayday, Manu Shankar-Hari
Manuel Mayr
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0597-829X
Clemens Gutmann
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
ORCiD: https://orcid.org/0000-0003-0675-8632
Kaloyan Takov
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
ORCiD: https://orcid.org/0000-0002-8642-6306
Sean Burnap
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
ORCiD: https://orcid.org/0000-0002-3408-8608
Bhawana Singh
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Konstantinos Theofilatos
King's College
ORCiD: https://orcid.org/0000-0001-6799-0553
Ella Reed
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Maria Hasman
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Adam Nabeebaccus
King's College Hospital NHS Foundation Trust, London
Matthew Fish
King's College London
ORCiD: https://orcid.org/0000-0001-6462-3889
Mark McPhail
Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London
Kevin O'Gallagher
King's College Hospital NHS Foundation Trust, London
Lukas Schmidt
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Christian Cassel
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
Marieke Rienks
King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, London
ORCiD: https://orcid.org/0000-0002-0590-9518
Xiaoke Yin
King's College London
ORCiD: https://orcid.org/0000-0002-5172-0935
Georg Auzinger
King's College Hospital NHS Foundation Trust, London
Salvatore Napoli
Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London
Salma Mujib
Institute of Liver Studies, King’s College Hospital, London
Francesca Trovato
King's College Hospital NHS Foundation Trust, London
Barnaby Sanderson
Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London
ORCiD: https://orcid.org/0000-0002-9621-143X
Blair Merrick
Guy's and St Thomas' NHS Foundation Trust
ORCiD: https://orcid.org/0000-0002-6061-6064
Umar Niazi
King's College London
ORCiD: https://orcid.org/0000-0001-7176-8883
Mansoor Saqi
NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust
Konstantina Dimitrakopoulou
NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London
Silke Braun
Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden
Romy Kronstein-Wiedemann
Medical Faculty Carl Gustav Carus, Technische Universität Dresden
Katie Doores
King's College London
ORCiD: https://orcid.org/0000-0002-5507-1725
Jonathan Edgeworth
5th Floor North Wing, St Thomas' Hospital, London, UK
Ajay Shah
King's College London
Stefan Bornstein
Medical Faculty Carl Gustav Carus at the Technical University of Dresden
Torsten Tonn
Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
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 was associated with higher 28-day ICU mortality (hazard ratio HR, 1.84 95% CI, 1.22–2.77 adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.