Figure 3. Distribution of total peak area of the chemical family in the control (CTRL, n = 42), COVID-19 (COVID, n = 61), and recovered (RECOV, n = 30) groups. The average peak areas were normalised areas obtained by the ratio between the peak areas of each VOM and the respective IS peak areas. ∑VOMs indicate the sum of different VOMs identified in each class; iVOMs indicate the number of VOMs identified in each recruited group and class. The RSD was less than 30%. Ter: Terpenes; PC: Phenolic Compounds; Nor: Norisoprenoids; Ket: Ketones; Alc: Alcohols; FC: Furanic Compounds; SC: Sulfur Compounds; ND: Naphthalene Derivatives; CA: Carboxylic Acid; Est: Esters; BD: Benzene Derivatives; Hc: Hydrocarbons; Ald: Aldehydes.
However, there were significant variations in the levels of these and less represented chemical families among the groups studied, with decreased levels of terpenes, phenolic compounds, benzene derivatives, hydrocarbons, and aldehydes in COVID-19 patients compared to the control subjects. In contrast, increased levels of norisoprenoids, ketones, alcohols, furans, sulfur compounds, and naphthalene derivatives were observed. For most chemical families in the RECOV group, the sum of the average peak areas was like that of the control group, except for benzene derivatives, terpenes, and phenolic compounds, whose levels were like the COVID-19 group. It should also be highlighted that the variations in the relative levels of the different chemical families are broadly caused by an increase in the decrease of the same VOMs, as the numbers for each chemical family in each group do not vary significantly. The only exceptions are ketones, with 10, 9, and 13 ketones identified in CTRL, COVID-19 and RECOV groups, respectively.
Volatile organic metabolites can have various origins. They can be endogenous because of bacterial activity or pH changes and can be the product of metabolic pathways or oxidative stress. They can be influenced by external factors including health status, diet, habits, physical stress, and environmental exposure. For these reasons, the human metabolome is highly complex, and it is difficult to understand whether an increase or decrease in certain metabolites is related to a specific disease or illness.
Therefore, it is crucial to establish a relationship between identified VOMs and their potential endogenous origins. However, the origin of many VOMs has not yet been clearly defined. Figure 4 shows the metabolomic pathways responsible for the origin of endogenous VOMs.