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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 non-invasive 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 compounds (VOCs) 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.

SUBMITTER: Berna AZ

PROVIDER: S-EPMC7743102 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFrom a public health perspective, the identification of individuals with mild respiratory symptoms due to SARS-CoV-2 infection is important to contain the spread of the disease. The objective of this study was to identify volatile organic compounds (VOCs) in exhaled breath common to infection with different variants of the SARS-CoV-2 virus to inform the development of a point-of-care breath test to detect infected individuals with mild symptoms.MethodsA prospective, real-world, observational study was conducted on mildly symptomatic out-patients presenting to community test-sites for RT-qPCR SARS-CoV-2 testing when the Alpha, Beta, and Delta variants were driving the COVID-19 pandemic. VOCs in exhaled breath were compared between PCR-positive and negative individuals using TD-GC-ToF-MS. Candidate VOCs were tested in an independent set of samples collected during the Omicron phase of the pandemic.FindingsFifty breath samples from symptomatic RT-qPCR positive and 58 breath samples from test-negative, but symptomatic participants were compared. Of the 50 RT-qPCR-positive participants, 22 had breath sampling repeated 8-12 weeks later. PCA-X model yielded 12 distinct VOCs that discriminated SARS-CoV-2 active infection compared to recovery/convalescence period, with an area under the receiver operator characteristic curve (AUROC), of 0.862 (0.747-0.977), sensitivity, and specificity of 82% and 86%, respectively. PCA-X model from 50 RT-qPCR positive and 58 negative symptomatic participants, yielded 11 VOCs, with AUROC of 0.72 (0.604-0.803) and sensitivity of 72%, specificity 65.5%. The 11 VOCs were validated in a separate group of SARS-CoV-2 Omicron positive patients' vs healthy controls demonstrating an AUROC of 0.96 (95% CI 0.827-0.993) with sensitivity of 80% specificity of 90%.InterpretationExhaled breath analysis is a promising non-invasive, point-of-care method to detect mild COVID-19 infection.FundingFunding for this study was a competitive grant awarded from the Vancouver Coastal Research Institute as well as funding from the BC Cancer Foundation.

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Reproducible breath metabolite changes in children with SARS-CoV-2 infection.

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