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.