A proteomic survival predictor for COVID-19 patients in intensive care
Journal article, 2022
Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.
Author
Vadim Demichev
University of Cambridge
The Francis Crick Institute
Charité University Medicine Berlin
Pinkus Tober-Lau
Charité University Medicine Berlin
Tatiana Nazarenko
University College London (UCL)
Oliver Lemke
Charité University Medicine Berlin
Simran Kaur Aulakh
The Francis Crick Institute
Harry Whitwell
Imperial College London
Lobachevsky University
Annika Röhl
Charité University Medicine Berlin
Anja Freiwald
Charité University Medicine Berlin
Mirja Mittermaier
Berliner Institut für Gesundheitsforschung
Charité University Medicine Berlin
Lukasz Szyrwiel
The Francis Crick Institute
Daniela Ludwig
Charité University Medicine Berlin
Clara Correia-Melo
The Francis Crick Institute
Lena J. Lippert
Charité University Medicine Berlin
Elisa T. Helbig
Charité University Medicine Berlin
Paula Stubbemann
Charité University Medicine Berlin
Nadine Olk
Charité University Medicine Berlin
Charlotte Thibeault
Charité University Medicine Berlin
Nana-Maria Grüning
Charité University Medicine Berlin
Oleg Blyuss
Sechenov First Moscow State Medical University
University of Hertfordshire
Lobachevsky University
Spyros I. Vernardis
The Francis Crick Institute
Matthew White
The Francis Crick Institute
Christoph B. Messner
The Francis Crick Institute
Charité University Medicine Berlin
Michael Joannidis
Department Innere Medizin, Innsbruck
Thomas Sonnweber
Medical University of Innsbruck
Sebastian J. Klein
Department Innere Medizin, Innsbruck
Alex Pizzini
Medical University of Innsbruck
Yvonne Wohlfarter
Medical University of Innsbruck
Sabina Sahanic
Medical University of Innsbruck
Richard Hilbe
Medical University of Innsbruck
Benedikt Schaefer
Medical University of Innsbruck
Sonja Wagner
Medical University of Innsbruck
Felix Machleidt
Charité University Medicine Berlin
Carmen Garcia
Charité University Medicine Berlin
Christoph Ruwwe-Glösenkamp
Charité University Medicine Berlin
Tilman Lingscheid
Charité University Medicine Berlin
Laure Bosquillon de Jarcy
Charité University Medicine Berlin
Miriam S. Stegemann
Charité University Medicine Berlin
Moritz Pfeiffer
Charité University Medicine Berlin
Linda Jürgens
Charité University Medicine Berlin
Sophy Denker
Charité University Medicine Berlin
Daniel Zickler
Charité University Medicine Berlin
Claudia Spies
Charité University Medicine Berlin
Andreas Edel
Charité University Medicine Berlin
Nils B. Müller
Charité University Medicine Berlin
Philipp Enghard
Charité University Medicine Berlin
Aleksej Zelezniak
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
The Francis Crick Institute
Rosa Bellmann-Weiler
Medical University of Innsbruck
Günter Weiss
Medical University of Innsbruck
Archie Campbell
University of Edinburgh
Edinburgh Medical School
Caroline Hayward
Edinburgh Medical School, Medical Research Council Human Genetics Unit
David J. Porteous
University of Edinburgh
Edinburgh Medical School
Riccardo E. Marioni
University of Edinburgh
Alexander Uhrig
Charité University Medicine Berlin
Heinz Zoller
Medical University of Innsbruck
Judith Löffler-Ragg
Medical University of Innsbruck
M. A. Keller
Medical University of Innsbruck
Ivan Tancevski
Medical University of Innsbruck
John F. Timms
University College London (UCL)
Alexey Zaikin
Sechenov First Moscow State Medical University
University College London (UCL)
Lobachevsky University
Stefan Hippenstiel
Charité University Medicine Berlin
German Centre for Lung Research
Michael Ramharter
Universitatsklinikum Hamburg-Eppendorf und Medizinische Fakultat
Holger Müller-Redetzky
Charité University Medicine Berlin
Martin Witzenrath
Charité University Medicine Berlin
German Centre for Lung Research
Norbert Suttorp
German Centre for Lung Research
Charité University Medicine Berlin
Kathryn S. Lilley
University of Cambridge
Michael Mülleder
Charité University Medicine Berlin
Leif Erik Sander
Charité University Medicine Berlin
German Centre for Lung Research
M. Ralser
Charité University Medicine Berlin
PLOS Digital Health
27673170 (eISSN)
Vol. 1 1 January e0000007Subject Categories
Anesthesiology and Intensive Care
DOI
10.1371/journal.pdig.0000007