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].