An Integrated Analysis and Comparison of Serum, Saliva and Sebum for COVID-19 Metabolomics

Abstract Non-invasive sampling approaches are desirable in healthcare settings due to the lower burden on patients and clinical staff. In the field of metabolomics, however, most studies have utilised blood serum or plasma. In this work 83 COVID-19 positive and negative hospitalised participants provided serum, saliva and sebum samples for analysis by mass spectrometry. Here we present the first comprehensive analysis of correlations between serum metabolites, salivary metabolites and sebum lipids, and consider their relative accuracy in differentiating COVID-19 positive participants from controls. Sebum lipids showed clear correlations to serum metabolites, with widespread changes to the serum-sebum lipid axis in COVID-19 positive participants, evidence of multi-organ dyslipidemia. In the COVID-19 positive cohort, correlations were notably marked between sebum lipids and the immunostimulatory hormone dehydroepiandrosterone sulphate. In terms of diagnostic accuracy, serum performed best by multivariate analysis (sensitivity and specificity of 0.97), with the dominant changes in triglyceride and bile acid levels, concordant with other studies identifying dyslipidemia as a hallmark of COVID-19 infection. Sebum diagnostic accuracy performed well (sensitivity 0.92; specificity 0.84), with saliva offering weaker diagnostic accuracy (sensitivity 0.78; specificity 0.83). These findings highlight the potential for integrated biofluid analyses to provide insight into the whole-body atlas of pathophysiological conditions.