Fig. 1

Plasma metabolome differences in SARS-CoV-2-infected and uninfected subjects. Order of importance of individual metabolites (in PLS-DA model) in SARS-CoV-2-uninfected (healthy control, orange bar) and SARS-CoV-2-infected (blue bar) subjects. A The four metabolites most significantly down-regulated in infected patients (relative to uninfected subjects). B The four most significant metabolites up-regulated in infected patients (red symbol) relative to uninfected subjects (black symbols). C Metabolic pathways identified by untargeted metabolomics in the plasma of SARS-CoV-2-uninfected subjects (black symbols) and SARS-CoV-2-infected patients (red symbols). D Purine metabolism: adenosine monophosphate can be converted to inosine either by (i) deamination to form inosine monophosphate followed by dephosphorylation or (ii) dephosphorylation to form adenosine followed by deamination. Hypoxanthine, formed from inosine, can undergo oxidative hydroxylation to xanthine which can then be converted by xanthine oxidase to uric acid. Allantoin is formed from the reaction between uric acid and reactive oxygen species (ROS). E Tryptophan metabolism: In the kynurenine pathway (which accounts for ~ 95% of tryptophan degradation), tryptophan forms kynurenine (by tryptophan-2,3-dioxygenase (TDO) or indoleamine 2,3-dioxygenase (IDO)). Kynurenine can then undergo hydroxylation to 3-hydroxy kynurenine (by kynurenine 3-monooxygenase (KMO)). A minor degradation pathway involves tryptophan hydroxylation to 5-hydroxy-tryptophan (by tryptophan hydroxylase isoforms 1 and 2 (TPH1/2)) and then to serotonin and melatonin (by aromatic-L-amino-acid decarboxylase (AAAD)). In figures B–E, data are presented as the mean ± SD and each dot represents individual sample results. Dots outside the box plot are in the upper quartile (75th percentile) of the distribution and the dots inside the box plot are in the interquartile range (IQR), where 50% of the data are located. Outside the box plot are the patients that are outside the IQR range. The box plot is divided at the median. Probability values reflect results in SARS-CoV-2-infected patients being compared with uninfected subjects using a Student’s unpaired t-test