Reproducible Breath Metabolite Changes in Children with SARS-CoV-2 Infection

Abstract

SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid noninvasive method to detect infection would be highly advantageous. Compelling evidence from canine biosensors and studies of adults with COVID-19 suggests that infection reproducibly alters human volatile organic compound (VOC) profiles. To determine whether pediatric infection is associated with VOC changes, we enrolled SARS-CoV-2 infected and uninfected children admitted to a major pediatric academic medical center. Breath samples were collected from children and analyzed through state-of-the-art GCxGC-ToFMS. Isolated features included 84 targeted VOCs. Candidate biomarkers that were correlated with infection status were subsequently validated in a second, independent cohort of children. We thus find that six volatile organic compounds are significantly and reproducibly increased in the breath of SARS-CoV-2 infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention, as aldehydes are also elevated in the breath of adults with COVID-19. Together, these biomarkers demonstrate high accuracy for distinguishing pediatric SARS-CoV-2 infection and support the ongoing development of novel breath-based diagnostics.

The potential of volatile organic compounds-based breath analysis for COVID-19 screening: a systematic review & meta-analysis.

“…Six articles were included with a total of 4,093 participants. Patients’ recruited in the studies are individuals with suggestive symptoms of COVID-19 ( Wintjens et al, 2020 , Grassin-Delyle et al, 2021 , Ruszkiewicz et al, 2020 , de et al, 2021 ); acute respiratory distress syndrome (ARDS) patients requiring mechanical ventilation ( Grassin-Delyle et al, 2021 ); COVID-19 patients confirmed with RT-PCR ( Berna et al, 2021 , Shan et al, 2020 ), computed tomography (CT) and laboratory (antibody test) ( Shan et al, 2020 ). The study participants were then grouped into two based on their COVID-19 status (positive or negative).…”

“…Methods used to detect VOCs vary between studies, as summarized in Table 1 , with some already used patented breath analyzing devices. Three studies analyzed chemical constituents of exhaled breath using GC-MS breath analysis ( Berna et al, 2021 , Grassin-Delyle et al, 2021 , Ruszkiewicz et al, 2020 ). Three other studies made use of the electronic nose with a pattern recognition method ( Wintjens et al, 2020 , de et al, 2021 , Shan et al, 2020 ).…”

“…Another device, MCC-IMS from STEP Sensortechnik, used by Ruszkiewicz et al requires patients to exhale slowly for 10 seconds into a foam cuffed oxygen catheter via filter ( Ruszkiewicz et al, 2020 ). Berna et al used a three-bed Universal sorbent tube and the patients were required to exhale through a disposable cardboard mouthpiece connected to a chamber ( Berna et al, 2021 ). Using a more complex, proton-transfer-reaction quadrupole time-of-flight mass spectrometer, Grassin-Delyle et al collected the samples through a heated transfer line connected directly to the end of an endotracheal tube ( Grassin-Delyle et al, 2021 ).…”

“…Six candidate breath biomarkers were significantly elevated in the breath of children with SARS-CoV-2 infection: three aldehydes (octanal, nonanal, and heptanal), as well as decane, tridecane, and 2-pentyl furan ( Berna et al, 2021 ). Grassin-Delyle et al (2021) identified elevated substances in COVID-19 suspected patients, such as methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal ( Grassin-Delyle et al, 2021 ).…”

“…Despite its high sensitivity and specificity, RT-PCR requires sophisticated facilities, complex, time-consuming procedures, and trained staff. Moreover, being an invasive sampling method, obtaining clinical samples is considered to be uncomfortable for the recipients ( Berna et al, 2021 ). Hence, it is considered unsuitable for a rapid and large-scale diagnosis ( Wintjens et al, 2020 ).…”