ABSTRACT
To assess whether SARS-CoV-2 infection induces changes in the urinary volatilomic fingerprint suitable for non-invasive COVID-19 diagnosis and management, urine samples from SARS-CoV-2 infected patients (62), recovered COVID-19 patients (30), and non-infected individuals (41), were analysed using solid-phase microextraction technique in headspace mode, combined with gas chromatography hyphenated with mass spectrometry (HS-SPME/GC-MS). A total of 101 volatile organic metabolites (VOMs) from 13 chemical families were characterized, with terpenes, phenolic compounds, norisoprenoids, and ketones being the most represented groups. Overall, the levels of terpenes and phenolic compounds decreased in the control group, whereas those of norisoprenoids and ketones increased significantly. In turn, a remarkable increase was noticed in norisoprenoids and ketones and a milder increase in alcohols, furanic, and sulfur compounds in the recovery group than in the COVID group. Multivariate statistical analysis identified sets of VOMs that could constitute the signatures of COVID-19 development and progression. These signatures are composed of D-carvone, 3-methoxy-5-(trifluoromethyl)aniline (MTA), 1,1,6-trimethyl-dihydronaphthalene (TDN), 2-heptanone, and 2,5,5,8a-tetramethyl-1,2,3,5,6,7,8,8-octahydro-1-naphthalenyl ester acetate (TONEA) for COVID-19 infection and nonanoic acid, α-terpinene, β-damascenone, α-isophorone, and trans-furan linalool for patients recovering from the disease. The study reported in the current article provides evidence that changes in the urinary volatilomic profile triggered by SARS-CoV-2 infection constitute a promising and valuable screening and/or diagnostic and management tool for COVID-19 in clinical environment.
Keywords: VOMs; urine; COVID-19; volatilomics; HS-SPME/GC-MS
1. INTRODUCTION
In late 2019, COVID-19, a highly infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a tremendous and severe pandemic outbreak. COVID-19 has been identified as a hyperinflammatory syndrome characterised by aberrant immune activation and excessive cytokine release (cytokine storm), ultimately leading to failure in multiple organs [1,2]. As the respiratory virus spread to all countries and/or regions in the world, intermittent lockdowns were imposed as a desperate and unprecedented measure to contain the propagation of the disease [3,4]. The effectiveness of this procedure is still an open debate, although it is widely acknowledged that the delay of virus propagation gave time to healthcare systems to adapt and mitigate the mortality caused by COVID-19 [4,5]. According to the World Health Organization (WHO), 768 million people were infected and over 6.94 million deaths have been estimated (Figure 1) [6]. This has caused a strong impact on society at economic, political, social, educational, environmental, and cultural levels that will last for decades [7-10].