Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection.

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Messner, Christoph B 
Demichev, Vadim 
Wendisch, Daniel 
Michalick, Laura 
White, Matthew 

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.

COVID-19 infection, SWATH-MS, antiviral immune response, clinical classifiers, high-throughput proteomics, mass spectrometry, Adult, Aged, Aged, 80 and over, Betacoronavirus, Biomarkers, Blood Proteins, COVID-19, Coronavirus Infections, Female, Humans, Male, Middle Aged, Pandemics, Pneumonia, Viral, Proteomics, SARS-CoV-2, Young Adult
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Cell Syst
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Elsevier BV
Biotechnology and Biological Sciences Research Council (BB/N015282/1)
Medical Research Council (MC_UU_12015/1)
MRC (MC_UU_00006/1)