Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

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.; Muelleder, M.; Drosten, C.; Witzenrath, M.; Kurth, F.; Sander, L. E.; Ralser, M.

The COVID-19 pandemic is an unprecedented global challenge. Highly variable in its presentation, spread and clinical outcome, novel point-of-care diagnostic classifiers are urgently required. Here, we describe a set of COVID-19 clinical classifiers discovered using a newly designed low-cost high-throughput mass spectrometry-based platform. Introducing a new sample preparation pipeline coupled with short-gradient high-flow liquid chromatography and mass spectrometry, our methodology facilitates clinical implementation and increases sample throughput and quantification precision. Providing a rapid assessment of serum or plasma samples at scale, we report 27 biomarkers that distinguish mild and severe forms of COVID-19, of which some may have potential as therapeutic targets. These proteins highlight the role of complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling upstream and downstream of Interleukin 6. Application of novel methodologies hence transforms proteomics from a research tool into a rapid-response, clinically actionable technology adaptable to infectious outbreaks.