Cell Systems
Volume 11, Issue 1, 22 July 2020, Pages 11-24.e4
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Article
Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection

https://doi.org/10.1016/j.cels.2020.05.012Get rights and content
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Highlights

  • A standardized, ultra-high-throughput clinical platform for serum and plasma proteomics

  • Platform enables high precision quantification of 180 human proteomes per day at low cost

  • 27 biomarkers are differentially expressed between WHO severity grades for COVID-19

  • Biomarkers include proteins not previously associated with COVID-19 infection

Summary

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.

Keywords

high-throughput proteomics
mass spectrometry
SWATH-MS
COVID-19 infection
clinical classifiers
antiviral immune response

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15

These authors contributed equally

16

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