Levels of 14 proteins in the blood of critically ill COVID-19 patients are associated with survival.
A single blood sample from a critically ill COVID-19 patient can be analyzed by a machine learning model which uses blood plasma proteins to predict survival, weeks before the outcome, according to a new study published this week in the open-access journal PLOS Digital Health by Florian Kurth and Markus Ralser of the Charité – Universitätsmedizin Berlin, Germany, and colleagues.
Healthcare systems around the world are struggling to accommodate high numbers of severely ill COVID-19 patients who need special medical attention, especially if they are identified as being at high risk. Clinically established risk assessments in intensive care medicine, such as the SOFA or APACHE II, show only limited reliability in predicting future disease outcomes for COVID-19.
In the new study, researchers studied the levels of 321 proteins in blood samples taken at 349 timepoints from 50 critically ill COVID-19 patients being treated in two independent health care centers in Germany and Austria. A machine learning approach was used to find associations between the measured proteins and patient survival.
15 of the patients in the cohort died; the average time from admission to death was 28 days. For patients who survived, the median time of hospitalization was 63 days. The researchers pinpointed 14 proteins which, over time, changed in opposite directions for patients who survive compared to patients who do not survive on intensive care. The team then developed a machine learning model to predict survival based on a single time-point measurement of relevant proteins and tested the model on an independent validation cohort of 24 critically ill COVID-10 patients. The model demonstrated high predictive power on this cohort, correctly predicting the outcome for 18 of 19 patients who survived and 5 out of 5 patients who died (AUROC = 1.0, P = 0.000047).
The researchers conclude that blood protein tests, if validated in larger cohorts, may be useful in both identifying patients with the highest mortality risk, as well as for testing whether a given treatment changes the projected trajectory of an individual patient.
Reference: “A proteomic survival predictor for COVID-19 patients in intensive care” by Vadim Demichev, Pinkus Tober-Lau, Tatiana Nazarenko, Oliver Lemke, Simran Kaur Aulakh, Harry J. Whitwell, Annika Röhl, Anja Freiwald, Mirja Mittermaier, Lukasz Szyrwiel, Daniela Ludwig, Clara Correia-Melo, Lena J. Lippert, Elisa T. Helbig, Paula Stubbemann, Nadine Olk, Charlotte Thibeault, Nana-Maria Grüning, Oleg Blyuss, Spyros Vernardis, Matthew White, Christoph B. Messner, Michael Joannidis, Thomas Sonnweber, Sebastian J. Klein, Alex Pizzini, Yvonne Wohlfarter, Sabina Sahanic, Richard Hilbe, Benedikt Schaefer, Sonja Wagner, Felix Machleidt, Carmen Garcia, Christoph Ruwwe-Glösenkamp, Tilman Lingscheid, Laure Bosquillon de Jarcy, Miriam S. Stegemann, Moritz Pfeiffer, Linda Jürgens, Sophy Denker, Daniel Zickler, Claudia Spies, Andreas Edel, Nils B. Müller, Philipp Enghard, Aleksej Zelezniak, Rosa Bellmann-Weiler, Günter Weiss, Archie Campbell, Caroline Hayward, David J. Porteous, Riccardo E. Marioni, Alexander Uhrig, Heinz Zoller, Judith Löffler-Ragg, Markus A. Keller, Ivan Tancevski, John F. Timms, Alexey Zaikin, Stefan Hippenstiel, Michael Ramharter, Holger Müller-Redetzky, Martin Witzenrath, Norbert Suttorp, Kathryn Lilley, Michael Mülleder, Leif Erik Sander, PA-COVID-19 Study group, Florian Kurth and Markus Ralser, 18 January 2022, PLOS Digital Health.