Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection
Open accessPublished version of a preprint
Abstract
The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.
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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 [67]
COVID-19 studies have measured various soluble factor panels, but few used comprehensive approaches.
“different combinations of soluble factors were assessed in different studies in context of COVID-19 with only a few choosing comprehensive approaches (Messner et al., 2020; Su et al., 2020).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Messner et al., 2020
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References 128 · Cited by 561
- Authors
- Messner, C. B., Demichev, V., Wendisch, D., Michalick, L., White, M., Freiwald, A., Textoris-Taube, K., Vernardis, S. I., Egger, A.-S., Kreidl, M., Ludwig, D., Kilian, C., Agostini, F., Zelezniak, A., Thibeault, C., Pfeiffer, M., Hippenstiel, S., Hocke, A., von Kalle, C., Campbell, A., Hayward, C., Porteous, D. J., Marioni, R. E., Langenberg, C., Lilley, K. S., Kuebler, W. M., Mülleder, M., Drosten, C., Suttorp, N., Witzenrath, M., Kurth, F., Sander, L. E., & Ralser, M.
- Affiliations
- The Francis Crick Institute (GB)
- University of Cambridge (GB)
- Charité – Universitätsmedizin Berlin (DE)
- Institute of Genetics and Cancer (GB)
- University of Edinburgh (GB)
- Corresponding author
- Ralser, Markus
- ORCID
- Messner, Christoph B.
- Demichev, Vadim
- Wendisch, Daniel
- Michalick, Laura
- White, Matthew
- Vernardis, Spyros I.
- Egger, Anna-Sophia
- Kreidl, Marco
- Agostini, Federica
- Zelezniak, Aleksej
- Thibeault, Charlotte
- Hippenstiel, Stefan
- Hocke, Andreas
- Campbell, Archie
- Hayward, Caroline
- Porteous, David J.
- Marioni, Riccardo E.
- Langenberg, Claudia
- Lilley, Kathryn S.
- Kuebler, Wolfgang M.
- Mülleder, Michael
- Drosten, Christian
- Suttorp, Norbert
- Witzenrath, Martin
- Kurth, Florian
- Sander, Leif Erik
- Ralser, Markus
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 11
- Issue
- 1
- Pages
- 11-24.e4
- ISSN
- 2405-4712 (ISSN-L)
- PMC
- PMC7264033
- OpenAlex
- W3031410640
- Cited by
- 561
- References
- 128
- Citations by year
- 2026: 37 · 2025: 38 · 2024: 80 · 2023: 95 · 2022: 115 · 2021: 139 · 2020: 54 · 2019: 1 · 2014: 1
- FWCI
- 38.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Berlin Institute of Health (SFB-TR84 C6)
- Medical Research Council (MC_UU_00007/10 ))
- Scottish Funding Council (HR03006)
- Biotechnology and Biological Sciences Research Council (10658, 1290305, 200829/Z/16/Z, BB/N015282/1, BB/ N015215/1)
- Chief Scientist Office, Scottish Government Health and Social Care Directorate (CZD/16/6)
- Francis Crick Institute
- Cancer Research UK
- LifeArc
- Bundesministerium für Bildung und Forschung (FKZ 01KI20160A, 01ZX1304B, FKZ 01ZX1906A)
- Deutsche Forschungsgemeinschaft (SFB-TR84 114933180)
- Wellcome Trust (216767/Z/19/Z, FC001134)
- Alzheimer’s Research UK (ARUK-PG2017B-10)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
- Keywords
- COVID-19 pandemic, SARS-CoV-2, serum proteomics, plasma proteomics, point-of-care testing, biomarkers, disease severity, complement system, coagulation system, inflammation, interleukin-6, clinical laboratory standardization, hospitalized patients
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Adult, Aged, Aged, 80 and over, Blood Proteins, Female, Humans, Male, Middle Aged, Pneumonia, Viral, Biomarkers, Coronavirus Infections, Proteomics, Young Adult, Pandemics
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