Discovery and systematic assessment of early biomarkers that predict progression to severe COVID-19 disease.

Background: The clinical course of COVID-19 patients ranges from asymptomatic infection, via mild and moderate illness, to severe disease and even fatal outcome. Biomarkers which enable an early prediction of the severity of COVID-19 progression, would be enormously beneficial to guide patient care and early intervention prior to hospitalization.

Methods: Here we describe the identification of plasma protein biomarkers using an antibody microarray-based approach in order to predict a severe cause of a COVID-19 disease already in an early phase of SARS-CoV-2 infection. To this end, plasma samples from two independent cohorts were analyzed by antibody microarrays targeting up to 998 different proteins.

Results: In total, we identified 11 promising protein biomarker candidates to predict disease severity during an early phase of COVID-19 infection coherently in both analyzed cohorts. A set of four (S100A8/A9, TSP1, FINC, IFNL1), and two sets of three proteins (S100A8/A9, TSP1, ERBB2 and S100A8/A9, TSP1, IFNL1) were selected using machine learning as multimarker panels with sufficient accuracy for the implementation in a prognostic test.

Conclusions: Using these biomarkers, patients at high risk of developing a severe or critical disease may be selected for treatment with specialized therapeutic options such as neutralizing antibodies or antivirals. Early therapy through early stratification may not only have a positive impact on the outcome of individual COVID-19 patients but could additionally prevent hospitals from being overwhelmed in potential future pandemic situations.