Published on Thu Jul 22 2021

Integrative Metabolomic and Proteomic Signatures Define Clinical Outcomes in Severe COVID-19

Alvarez-Mulett, S., Buyukozkan, M., Racanelli, A. C., Schmidt, F., Batra, R., Hoffman, K. L., Sarwath, H., Engelke, R., Gomez-Escobar, L., Simmons, W., Benedetti, E., Chetnik, K., Schenck, E., Suhre, K., Choi, J. J., Zhao, Z., Racine-Brzostek, S., Yang, H. S., Choi, M. E., Choi, A. M. K., Cho, S. J., Krumsiek, J.

The novel coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has ravaged global healthcare with previously unseen levels of morbidity and mortality. To date, methods to predict the clinical course have yet to be identified.

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Abstract

The novel coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has ravaged global healthcare with previously unseen levels of morbidity and mortality. To date, methods to predict the clinical course, which ranges from the asymptomatic carrier to the critically ill patient in devastating multi-system organ failure, have yet to be identified. In this study, we performed large-scale integrative multi-omics analyses of serum obtained from COVID-19 patients with the goal of uncovering novel pathogenic complexities of this disease and identifying molecular signatures that predict clinical outcomes. We assembled a novel network of protein-metabolite interactions in COVID-19 patients through targeted metabolomic and proteomic profiling of serum samples in 330 COVID-19 patients compared to 97 non-COVID, hospitalized controls. Our network identified distinct protein-metabolite cross talk related to immune modulation, energy and nucleotide metabolism, vascular homeostasis, and collagen catabolism. Additionally, our data linked multiple proteins and metabolites to clinical indices associated with long-term mortality and morbidity, such as acute kidney injury. Finally, we developed a novel composite outcome measure for COVID-19 disease severity and created a clinical prediction model using a set of 33 metabolites. The model significantly improved the identification of key events of critical illness such as prolonged hospitalization, supplemental oxygen requirement, acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS), beyond those achieved using the more traditional risk factors of age, gender, and BMI.