A time-resolved proteomic and prognostic map of COVID-19
Open accessAbstract
COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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SASP-typical cytokines, extracellular matrix-active proteases, and SASP-related pro-coagulant and complement-activating factors are strongly elevated in the serum of COVID-19 patients compared with healthy controls.
“were also strongly elevated in the serum of patients with COVID-19 compared to healthy controls28,52,67–70.”
From COVID-19 and cellular senescence (2023) · cites this paper as [68]
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Large-scale Multi-omic Analysis of COVID-19 SeverityPreprint
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Coronavirus Disease 2019 (COVID-19): Epidemiology, Pathogenesis, Diagnosis, and Therapeutics
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Apolipoprotein D: An overview of its role in aging and age-related diseases
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Platelet-derived β2M regulates monocyte inflammatory responses
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A neutrophil activation signature predicts critical illness and mortality in COVID-19Preprint
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Self-citationVaccines and Therapies in Development for SARS-CoV-2 Infections
Wu, D. B.-C., Koganti, R., Lambe, U. P., Yadavalli, T., Nandi, S. S., & Shukla, D. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9061885 · Cited by 46 · see citing works
Immune response in bacterial and Candida sepsis
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New Insights into the Functions of Histidine-Rich Glycoprotein
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The Protective Arm of the Renin Angiotensin System (RAS)
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MRMAssayDB: an integrated resource for validated targeted proteomics assays
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A polipoprotein E Levels in Pediatric Patients Undergoing Cardiopulmonary Bypass
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Regulation of Neutrophil Serine Proteases by Intracellular Serpins
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Flagged first, then by citations
Research works printed but not linked: 1
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Cited by
Sorted by citations
Virus-induced senescence is a driver and therapeutic target in COVID-19
Lee, S., Yu, Y., Trimpert, J., Benthani, F., Mairhofer, M., Richter-Pechanska, P., Wyler, E., Belenki, D., Kaltenbrunner, S., Pammer, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03995-1 · Cited by 350 · see citing works
Self-citationComplement activation induces excessive T cell cytotoxicity in severe COVID-19
Georg, P., Astaburuaga-García, R., Bonaguro, L., Brumhard, S., Michalick, L., Lippert, L. J., Kostevc, T., Gäbel, C., Schneider, M., Streitz, M., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.040 · Cited by 218 · see citing works
Self-citationCOVID-19 and cellular senescence
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- Authors
- Demichev, V., Tober-Lau, P., Lemke, O., Nazarenko, T., Thibeault, C., Whitwell, H., Röhl, A., Freiwald, A., Szyrwiel, L., Ludwig, D., Correia-Melo, C., Aulakh, S. K., Helbig, E. T., Stubbemann, P., Lippert, L. J., Grüning, N.-M., Blyuss, O., Vernardis, S., White, M., Messner, C. B., Joannidis, M., Sonnweber, T., Klein, S. J., Pizzini, A., Wohlfarter, Y., Sahanic, S., Hilbe, R., Schaefer, B., Wagner, S., Mittermaier, M., Machleidt, F., Garcia, C., Ruwwe-Glösenkamp, C., Lingscheid, T., Bosquillon de Jarcy, L., Stegemann, M. S., Pfeiffer, M., Jürgens, L., Denker, S., Zickler, D., Enghard, P., Zelezniak, A., Campbell, A., Hayward, C., Porteous, D. J., Marioni, R. E., Uhrig, A., Müller-Redetzky, H., Zoller, H., Löffler-Ragg, J., Keller, M. A., Tancevski, I., Timms, J. F., Zaikin, A., Hippenstiel, S., Ramharter, M., Witzenrath, M., Suttorp, N., Lilley, K., Mülleder, M., Sander, L. E., Kleinschmidt, M., Heim, K. M., Millet, B., Meyer-Arndt, L., Hübner, R. H., Andermann, T., Doehn, J. M., Opitz, B., Sawitzki, B., Grund, D., Radünzel, P., Schürmann, M., Zoller, T., Alius, F., Knape, P., Breitbart, A., Li, Y., Bremer, F., Pergantis, P., Schürmann, D., Temmesfeld-Wollbrück, B., Wendisch, D., Brumhard, S., Haenel, S. S., Conrad, C., Georg, P., Eckardt, K.-U., Lehner, L., Kruse, J. M., Ferse, C., Körner, R., Spies, C., Edel, A., Weber-Carstens, S., Krannich, A., Zvorc, S., Li, L., Behrens, U., Schmidt, S., Rönnefarth, M., Dang-Heine, C., Röhle, R., Lieker, E., Kretzler, L., Wirsching, I., Wollboldt, C., Wu, Y., Schwanitz, G., Hillus, D., Kasper, S., Olk, N., Horn, A., Briesemeister, D., Treue, D., Hummel, M., Corman, V. M., Drosten, C., von Kalle, C., Ralser, M., & Kurth, F.
- Affiliations
- University of Cambridge (GB)
- Charité – Universitätsmedizin Berlin (DE)
- University College London (GB)
- Imperial College London (GB)
- The Francis Crick Institute (GB)
- University of Hertfordshire (GB)
- Innsbruck Medical University (AT)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Institute of Genetics and Cancer (GB)
- German Center for Lung Research (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Ralser, Markus
- ORCID
- Demichev, Vadim
- Lemke, Oliver
- Nazarenko, Tatiana
- Thibeault, Charlotte
- Whitwell, Harry
- Röhl, Annika
- Aulakh, Simran Kaur
- Helbig, Elisa T.
- Lippert, Lena J.
- Grüning, Nana-Maria
- Blyuss, Oleg
- Vernardis, Spyros
- White, Matthew
- Messner, Christoph B.
- Joannidis, Michael
- Sonnweber, Thomas
- Klein, Sebastian J.
- Pizzini, Alex
- Wohlfarter, Yvonne
- Sahanic, Sabina
- Hilbe, Richard
- Schaefer, Benedikt
- Wagner, Sonja
- Mittermaier, Mirja
- Machleidt, Felix
- Lingscheid, Tilman
- Stegemann, Miriam S.
- Denker, Sophy
- Zickler, Daniel
- Enghard, Philipp
- Zelezniak, Aleksej
- Campbell, Archie
- Hayward, Caroline
- Porteous, David J.
- Marioni, Riccardo E.
- Uhrig, Alexander
- Müller-Redetzky, Holger
- Zoller, Heinz
- Keller, Markus A.
- Tancevski, Ivan
- Timms, John F.
- Zaikin, Alexey
- Hippenstiel, Stefan
- Ramharter, Michael
- Suttorp, Norbert
- Lilley, Kathryn
- Mülleder, Michael
- Sander, Leif Erik
- Hübner, Ralf H.
- Opitz, Bastian
- Sawitzki, Birgit
- Grund, Daniel
- Knape, Philipp
- Pergantis, Panagiotis
- Schürmann, Dirk
- Wendisch, Daniel
- Brumhard, Sophia
- Georg, Philipp
- Eckardt, Kai-Uwe
- Lehner, Lukas
- Kruse, Jan M.
- Spies, Claudia
- Edel, Andreas
- Krannich, Alexander
- Li, Linna
- Schmidt, Sein
- Rönnefarth, Maria
- Röhle, Robert
- Lieker, Emma
- Kretzler, Lucie
- Wirsching, Isabelle
- Wu, Yinan
- Hillus, David
- Olk, Nadine
- Briesemeister, Dana
- Treue, Denise
- Hummel, Michael
- Corman, Victor M.
- Drosten, Christian
- Ralser, Markus
- Kurth, Florian
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 12
- Issue
- 8
- Pages
- 780-794.e7
- ISSN
- 2405-4712 (ISSN-L)
- PMC
- PMC8201874
- OpenAlex
- W3171623624
- Cited by
- 200
- References
- 117
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 45 · 2023: 44 · 2022: 60 · 2021: 15
- FWCI
- 13.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- University of Hertfordshire Research Archive (University of Hertfordshire) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo
- Apollo (cc-by)
- The Francis Crick Institute (cc-by)
- Funders
- Francis Crick Institute
- UK Research and Innovation
- Wellcome Trust (200829/Z/16/Z)
- Scottish Funding Council (216767/Z/19/Z, HR03006)
- BMBF Berlin
- Medical Research Council (MC_UU_00007/10 ), MR/R02524X/1)
- Österreichische Forschungsförderungsgesellschaft (878654)
- Biotechnology and Biological Sciences Research Council (BB/N015215/1, BB/N015282/1)
- National Institute for Health and Care Research
- Cancer Research UK (FC001134)
- NIHR Imperial Biomedical Research Centre
- Berlin Institute of Health (C09, SFB-TR84 C06)
- Berlin University Alliance
- Austrian Science Fund (P33333)
- European Research Council (SyG 951475)
- Deutsche Forschungsgemeinschaft (SFB-TR84 114933180)
- Alzheimer’s Research UK (ARUK-PG2017B-10)
- Bundesministerium für Bildung und Forschung (01ZX1304B)
- Charité – Universitätsmedizin Berlin
- Deutsches Zentrum für Luft- und Raumfahrt (01KI20160A, 01KI20337, 01KX2021, 01ZX1604B)
- Ministerstwo Edukacji i Nauki (075-15-2020-808)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- COVID-19 pandemic, plasma proteome, time-resolved proteomics, disease progression, systemic inflammation, prognostic factors, tissue repair, immunomodulation, machine learning classification, model transferability, SARS-CoV-2
- MeSH terms
- Machine Learning, COVID-19, SARS-CoV-2, Age Factors, Blood Cell Count, Blood Gas Analysis, Enzyme Activation, Humans, Inflammation, Prognosis, Biomarkers, Disease Progression, Proteome, Proteomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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