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A proteomic survival predictor for COVID-19 patients in intensive care.

Published version
Peer-reviewed

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Authors

Tober-Lau, Pinkus 
Lemke, Oliver 
Kaur Aulakh, Simran  ORCID logo  https://orcid.org/0000-0002-1580-7144

Abstract

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.

Description

Keywords

PA-COVID-19 Study group

Journal Title

PLOS Digit Health

Conference Name

Journal ISSN

2767-3170
2767-3170

Volume Title

1

Publisher

Public Library of Science (PLoS)
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/N015282/1)