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

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.