Glycolithocholic Acid 3-Sulfate as Serum Biomarker for Disease Severity and Mortality in COVID-19 Patients: Mass Spectrometry Approach

Background: Currently, there is no clinically established method to predict critically ill Coronavirus Disease -19 (COVID-19) patients. Few prognostic biomarkers are available to predict severe outcomes of patients and then differentiate customized therapies.Methods: We performed an untargeted metabolomics study in 15 serum samples of COVID-19 - survivor patients to establish potential severity biomarkers. Then, a targeted metabolomics study was performed on a larger patient cohort, including 15 non-survivors, at different time points (T1-T2-T3) during the disease course. The results were interpreted by performing univariate and multivariate analyses.Finding: Serum glycolithocholic acid 3- sulfate (GLCA-3S) was increased with a significant difference between survivors and non-survivors in the early stage of the illness (T1 p-value < 0 ·0001), highly correlated with mortality (p-value <0·001). The specificity and sensitivity values of GLCA-3S for predicting early clinical diagnosis were 80·0% and 85·7%, respectively. PLS-DA model was able to identify with high selectivity the most critical patients in the early stages of COVID-19.Interpretation: This study identifies sulfated bile acids (BA-S) as biomarkers with altered serum levels in a cohort of COVID-19 patients. Moreover, increased BA-S are highly correlated with the well-known parameters altered in the worse clinical conditions of COVID-19 patients. GLCA-3S was identified as the main biomarker correlated with mortality in the early stage of the illness.Funding Information: We acknowledge support from the Ministry of Education, University and Research of Italy: PRIN 2017 (Project 2017Y2PAB8) and the EU Horizon 2020 program INFRAIA project Epic-XS (Project 823839).Declaration of Interests: No competing interests.Ethics Approval Statement: The studies involving human participants were reviewed and approved by Comitato Etico Area Vasta Emilia Centro, Bologna, Italy. The patients/participants provided their written informed consent to participate in this study. In case of unconsciousness, the informed consent was signed by the next of kin or legal authorized representative.