Identification of a characteristic VOCs pattern in the exhaled breath of post-COVID subjects: are metabolic alterations induced by the infection still detectable?

SARS-CoV-2 is expected to cause metabolic alterations due to viral replication and the host immune response resulting in increase of cytokine secretion and cytolytic activity. The present prospective observational study is addressed at exploring the potentialities of breath analysis in discrimination between patients with a documented previous history of symptomatic SARS-CoV-2 infection and, at the moment of the enrollment, exhibiting a negative nasopharyngeal swab and acquired immunity (post-COVID) and healthy subjects with no evidence of previous SARS-CoV-2 infection (no-COVID). The main purpose is to understand if traces of metabolic alterations induced during the acute phase of the infection are still detectable after negativization, in the form of a characteristic volatile organic compound (VOC) pattern. An overall number of 60 volunteers aged between 25 and 70 years were enrolled in the study (post-COVID: n.30; no-COVID: n. 30), according to well-determined criteria. Breath and ambient air samples were collected by means of an automated sampling system (Mistral) and analyzed by thermal desorption-gas chromatography-mass spectrometry (TD-GC/MS). Statistical tests (Wilcoxon/Kruskal-Wallis test) and multivariate data analysis (principal component analysis (PCA), linear discriminant analysis) were performed on data sets. Among all compounds detected (76 VOCs in 90% of breath samples), 5 VOCs (1-propanol, isopropanol, 2-(2-butoxyethoxy)ethanol, propanal and 4-(1,1-dimethylpropyl)phenol) showed abundances in breath samples collected from post-COVID subjects significantly different with respect to those collected from no-COVID group (Wilcoxon/Kruskal-Wallis test, p-values <0.05). Although not completely satisfactory separation between the groups was obtained, variables showing significant differences between the two groups and higher loadings for PCA are recognized biomarkers of COVID-19, according to previous studies in literature. Therefore, based on the outcomes obtained, traces of metabolic alterations induced by SARS-CoV-2 infection are still detectable after negativization. This evidence raises questions about the eligibility of post-COVID subjects in observational studies addressed at the detection of COVID-19. (Ethical Committee Registration number: 120/AG/11).