An integrated analysis and comparison of serum, saliva and sebum for COVID-19 metabolomics

Abstract

The majority of metabolomics studies to date have utilised blood serum or plasma, biofluids that do not necessarily address the full range of patient pathologies. Here, correlations between serum metabolites, salivary metabolites and sebum lipids are studied for the first time. 83 COVID-19 positive and negative hospitalised participants provided blood serum alongside saliva and sebum samples for analysis by liquid chromatography mass spectrometry. Widespread alterations to serum-sebum lipid relationships were observed in COVID-19 positive participants versus negative controls. There was also a marked correlation between sebum lipids and the immunostimulatory hormone dehydroepiandrosterone sulphate in the COVID-19 positive cohort. The biofluids analysed herein were also compared in terms of their ability to differentiate COVID-19 positive participants from controls; 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 performed well (sensitivity 0.92; specificity 0.84), with saliva performing worst (sensitivity 0.78; specificity 0.83). These findings show that alterations to skin lipid profiles coincide with dyslipidaemia in serum. The work also signposts the potential for integrated biofluid analyses to provide insight into the whole-body atlas of pathophysiological conditions.

Untargeted saliva metabolomics by liquid chromatography—Mass spectrometry reveals markers of COVID-19 severity

“…This meant no scope for abstinence from food and / or drink before saliva sampling, and no prior rinsing of the mouth, leading to potential confounding factors. Diagnostic sensitivity of 0.74 (95% confidence interval of 0.60–0.86) and specificity of 0.75 (0.55–0.89) was considered insufficient to justify further investigation, given that proteomic and serum / plasma based metabolomic diagnostic tests have shown markedly better performance in diagnosing COVID-19 by both meta-analysis and in a recent matched-sample study [ 8 , 31 ]. Fig 4 illustrates that a more marked separation exists between low severity and high severity, than between hospital-recruited controls and low severity.…”

Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment

“…The objective of this study was to quantitatively investigate the serum metabolome, lipidome and proteome of hospital inpatients with COVID-19 to identify the combined influence of glucocorticoid treatment and COVID-19 infection, benefiting from the additional insight offered by combining multiple ‘omics approaches [ 23 , 24 ]. Because glucocorticoids were not prescribed for SARS-CoV-2 infections during the initial wave of COVID-19 in the UK (March to June 2020) but were widely prescribed in the second wave (July 2020 onwards), there is a time component which was not controlled for in this retrospective observational study, including the presence in the UK of new variants [ 25 , 26 , 27 ].…”

Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

“…In terms of the nature of the specimen, serum and plasma followed by urine ( Kurano et al, 2022b ; Kida et al, 2022 ) are the most studied biofluids, while other samples also scrutinized include saliva ( Spick et al, 2022b ; Frampas et al, 2022 ; Saheb Sharif-Askari et al, 2022 ), faeces ( He et al, 2021 ; Lv et al, 2021 ; Ren et al, 2021 ), platelets ( Schuurman et al, 2022 ), exhaled breath ( Barberis et al, 2021a ; Grassin-Delyle et al, 2021 ; Bennet et al, 2022 ; Remy et al, 2022 ), sebum from skin ( Spick et al, 2021 ) and breastmilk ( Zhao et al, 2020 ). Due to the high volume of information ( Table 1 ), we here complement other recent reviews on COVID-19 metabolomics ( Hasan et al, 2021 ; Lin et al, 2021 ; Costanzo et al, 2022 ) by selecting a set of contributions to be discussed in the present review, based on our evaluation of novelty, impact and originality.…”