ArticlePLOS digital health2022
A proteomic survival predictor for COVID-19 patients in intensive care.
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Article in PLOS digital health, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
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Who cites it
33 citing papers in PubMed.
- Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.Annals of medicine · 2026Article
- Pre-ECMO characteristics, organ dysfunction and exploratory mortality prediction in COVID-19 versus non-COVID-19 ARDS treated with veno-venous ECMO: a retrospective cohort study.BMC anesthesiology · 2026Article
- Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.Clinical proteomics · 2026Review
- Combining label-free Raman spectroscopy and machine learning to identify early biomarkers of COVID-19 disease severity and mortality.Journal of biomedical optics · 2026Article
- Innate Immune Evasion of Lyme Disease Pathogen Drives Alzheimer-Like Pathology.Research square · 2026Article
- Proteomic predictors of mortality among people with Coronary Artery Disease.American journal of preventive cardiology · 2025Article
- AHDSN: an attention-enabled hybrid deep sequential network for cancer survivability prediction from multi-omics data.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Proteomics and Metabolomics Profiles of Unvaccinated Nonagenarian Patients with Severe SARS-CoV-2 Infection.Journal of proteome research · 2025Article
- Plasma Proteomics Reveals Distinct Signatures in Occult and Microfilaremic Loa loa Infections.The Journal of infectious diseases · 2025Article
- Multiplex Targeted Proteomic Analysis of Cytokine Ratios for ICU Mortality in Severe COVID-19.Proteomes · 2025Article
- The Plasma Proteome and Risk of Future Venous Thromboembolism-Results from the HUNT Study in Thrombosis and Haemostasis.Thrombosis and haemostasis · 2025Article
- Differences in biomarker levels and proteomic survival prediction across two COVID-19 cohorts with distinct treatments.iScience · 2025Article
- Identification of Gene Signatures Associated with COVID-19 across Children, Adolescents, and Adults in the Nasopharynx and Peripheral Blood by Using a Machine Learning Approach.Current gene therapy · 2025Article
- The Circulating Proteome─Technological Developments, Current Challenges, and Future Trends.Journal of proteome research · 2024Article
- Delineating sex-specific circulating host response signatures associated with COVID-19 severity and mortality.iScience · 2024Article
- Longitudinal plasma proteomic analysis of 1117 hospitalized patients with COVID-19 identifies features associated with severity and outcomes.Science advances · 2024Article
- A reduced proteomic signature in critically ill Covid-19 patients determined with plasma antibody micro-array and machine learning.Clinical proteomics · 2024Article
- Oxonium ion scanning mass spectrometry for large-scale plasma glycoproteomics.Nature biomedical engineering · 2024Article
- Complex changes in serum protein levels in COVID-19 convalescents.Scientific reports · 2024Article
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Authors and funding
70 authors.
Vadim DemichevCharité-Universitätsmedizin Berlin, Department of Biochemistry, Berlin, Germany.ORCID https://orcid.org/0000-0002-2424-9412
Pinkus Tober-LauCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Tatiana NazarenkoUniversity College London, Department of Mathematics, London, United Kingdom.ORCID https://orcid.org/0000-0002-4245-7346
Oliver LemkeCharité-Universitätsmedizin Berlin, Department of Biochemistry, Berlin, Germany.
Simran Kaur AulakhThe Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, United Kingdom.ORCID https://orcid.org/0000-0002-1580-7144
Harry J WhitwellNational Phenome Centre and Imperial Clinical Phenotyping Centre, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.ORCID https://orcid.org/0000-0001-8987-4158
Annika RöhlCharité-Universitätsmedizin Berlin, Department of Biochemistry, Berlin, Germany.ORCID https://orcid.org/0000-0003-3924-6422
Anja FreiwaldCharité-Universitätsmedizin Berlin, Department of Biochemistry, Berlin, Germany.
Mirja MittermaierCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0003-0678-6676
Lukasz SzyrwielThe Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, United Kingdom.ORCID https://orcid.org/0000-0003-1983-2950
Daniela LudwigCharité-Universitätsmedizin Berlin, Department of Biochemistry, Berlin, Germany.
Clara Correia-MeloThe Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, United Kingdom.ORCID https://orcid.org/0000-0001-6062-1472
Lena J LippertCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0002-8337-1311
Elisa T HelbigCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0003-4276-7974
Paula StubbemannCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Nadine OlkCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Charlotte ThibeaultCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0002-8979-9386
Nana-Maria GrüningCharité-Universitätsmedizin Berlin, Department of Biochemistry, Berlin, Germany.ORCID https://orcid.org/0000-0002-1528-6625
Oleg BlyussLobachevsky University, Department of Applied Mathematics, Nizhny Novgorod, Russia.ORCID https://orcid.org/0000-0002-0194-6389
Spyros VernardisThe Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, United Kingdom.ORCID https://orcid.org/0000-0002-3946-1686
Matthew WhiteThe Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, United Kingdom.ORCID https://orcid.org/0000-0003-0923-974X
Christoph B MessnerCharité-Universitätsmedizin Berlin, Department of Biochemistry, Berlin, Germany.
Michael JoannidisMedical University Innsbruck, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Innsbruck, Austria.
Thomas SonnweberMedical University of Innsbruck, Department of Internal Medicine II, Innsbruck, Austria.
Sebastian J KleinMedical University Innsbruck, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Innsbruck, Austria.
Alex PizziniMedical University of Innsbruck, Department of Internal Medicine II, Innsbruck, Austria.ORCID https://orcid.org/0000-0003-3699-1822
Yvonne WohlfarterMedical University of Innsbruck, Institute of Human Genetics, Innsbruck, Austria.ORCID https://orcid.org/0000-0002-0988-9411
Sabina SahanicMedical University of Innsbruck, Department of Internal Medicine II, Innsbruck, Austria.
Richard HilbeMedical University of Innsbruck, Department of Internal Medicine II, Innsbruck, Austria.ORCID https://orcid.org/0000-0001-9987-109X
Benedikt SchaeferMedical University of Innsbruck, Christian Doppler Laboratory for Iron and Phosphate Biology, Department of Internal Medicine I, Innsbruck, Austria.ORCID https://orcid.org/0000-0001-8690-2774
Sonja WagnerMedical University of Innsbruck, Christian Doppler Laboratory for Iron and Phosphate Biology, Department of Internal Medicine I, Innsbruck, Austria.ORCID https://orcid.org/0000-0003-2319-2722
Felix MachleidtCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0002-6108-5269
Carmen GarciaCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0002-6859-1084
Christoph Ruwwe-GlösenkampCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0001-5077-829X
Tilman LingscheidCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0001-5377-3152
Laure Bosquillon de JarcyCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Miriam S StegemannCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0002-7968-0429
Moritz PfeifferCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Linda JürgensCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Sophy DenkerCharité-Universitätsmedizin Berlin, Medical Department of Hematology, Oncology & Tumor Immunology, Virchow Campus & Molekulares Krebsforschungszentrum, Berlin, Germany.ORCID https://orcid.org/0000-0002-0736-6019
Daniel ZicklerCharité-Universitätsmedizin Berlin, Department of Nephrology and Internal Intensive Care Medicine, Berlin, Germany.
Claudia SpiesCharité-Universitätsmedizin Berlin, Department of Anesthesiology and Intensive Care, Berlin, Germany.
Andreas EdelCharité-Universitätsmedizin Berlin, Department of Anesthesiology and Intensive Care, Berlin, Germany.ORCID https://orcid.org/0000-0002-9951-7223
Nils B MüllerCharité-Universitätsmedizin Berlin, Department of Nephrology and Internal Intensive Care Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0001-8918-857X
Philipp EnghardCharité-Universitätsmedizin Berlin, Department of Nephrology and Internal Intensive Care Medicine, Berlin, Germany.
Aleksej ZelezniakThe Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, United Kingdom.ORCID https://orcid.org/0000-0002-3098-9441
Rosa Bellmann-WeilerMedical University of Innsbruck, Department of Internal Medicine II, Innsbruck, Austria.ORCID https://orcid.org/0000-0002-5584-111X
Günter WeissMedical University of Innsbruck, Department of Internal Medicine II, Innsbruck, Austria.
Archie CampbellUniversity of Edinburgh, Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, United Kingdom.ORCID https://orcid.org/0000-0003-0198-5078
Caroline HaywardUniversity of Edinburgh, MRC Human Genetics Unit, Institute of Genetics and Cancer, Edinburgh, United Kingdom.ORCID https://orcid.org/0000-0002-9405-9550
David J PorteousUniversity of Edinburgh, Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, United Kingdom.ORCID https://orcid.org/0000-0003-1249-6106
Riccardo E MarioniUniversity of Edinburgh, Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, United Kingdom.
Alexander UhrigCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0001-7474-6743
Heinz ZollerMedical University of Innsbruck, Christian Doppler Laboratory for Iron and Phosphate Biology, Department of Internal Medicine I, Innsbruck, Austria.ORCID https://orcid.org/0000-0003-1794-422X
Judith Löffler-RaggMedical University of Innsbruck, Department of Internal Medicine II, Innsbruck, Austria.
Markus A KellerMedical University of Innsbruck, Institute of Human Genetics, Innsbruck, Austria.ORCID https://orcid.org/0000-0002-8654-9920
Ivan TancevskiMedical University of Innsbruck, Department of Internal Medicine II, Innsbruck, Austria.ORCID https://orcid.org/0000-0001-5116-8960
John F TimmsUniversity College London, Department of Women's Cancer, EGA Institute for Women's Health, London, United Kingdom.
Alexey ZaikinUniversity College London, Department of Mathematics, London, United Kingdom.ORCID https://orcid.org/0000-0001-7540-1130
Stefan HippenstielCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Michael RamharterBernhard Nocht Institute for Tropical Medicine, Department of Tropical Medicine, and University Medical Center Hamburg-Eppendorf, Department of Medicine, Hamburg, Germany.ORCID https://orcid.org/0000-0002-9259-1885
Holger Müller-RedetzkyCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Martin WitzenrathCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0002-9787-5633
Norbert SuttorpCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
Kathryn LilleyThe University of Cambridge, Department of Biochemistry and Cambridge Centre for Proteomics, Cambridge, United Kingdom.
Michael MüllederCharité-Universitätsmedizin Berlin, Core Facility-High-Throughput Mass Spectrometry, Berlin, Germany.ORCID https://orcid.org/0000-0001-9792-3861
Leif Erik SanderCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0002-0476-9947
PA-COVID-19 Study group
Florian KurthCharité-Universitätsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.ORCID https://orcid.org/0000-0002-3807-473X
Markus RalserCharité-Universitätsmedizin Berlin, Department of Biochemistry, Berlin, Germany.
Funding
Austrian Science Fund FWF P 33333Cancer Research UK FC001134Medical Research Council MC_UU_00007/10Medical Research Council MR/R02524X/1Wellcome Trust 200829/Z/16/ZWellcome Trust FC001134
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.
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