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

TLDR

The COVID‑19 pandemic demands rapid point‑of‑care diagnostic classifiers. We present an ISO13485‑standardized ultra‑high‑throughput proteomics platform to enable routine clinical assays that aid decision‑making and generate therapeutic hypotheses for COVID‑19. Our low‑cost workflow processes up to 180 samples per day, delivers high‑precision quantification, reduces batch effects, and was applied to early hospitalized COVID‑19 cases to identify biomarkers. We identified 27 biomarkers—including complement, coagulation, inflammation modulators, and IL‑6 upstream/downstream factors—associated with WHO severity grade, and made all protocols and software freely available.

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.