Breath biomarkers of pediatric SARS-CoV-2 infection: a pilot study

COVID-19 control efforts have been hampered by transmission from pre-symptomatic individuals infected with SARS-CoV2. Prolonged asymptomatic respiratory viral shedding in children has been described and may be another important reservoir for ongoing transmission. The primary diagnostic approach to identify SARS-CoV2 infection relies on qPCR of specific viral sequences from respiratory samples, which is expensive, uncomfortable, relatively slow, and susceptible to false-negative results. A rapid non-invasive method to detect mild or asymptomatic infection would have a major impact on public health campaigns to control COVID-19. We hypothesize that candidate biomarkers characterize the exhaled breath of children with SARS-CoV2 infection. To test this hypothesis, we enrolled SARS-CoV-2-infected and -uninfected children admitted to a major pediatric academic medical center and analyzed their breath volatile composition. Targeted volatiles analysis revealed that six volatile organic compounds increased significantly in SARS-CoV-2-infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention as candidate biomarkers, because viral infections have previously been shown to induce aldehyde production. Together, these biomarkers demonstrated 100% sensitivity and 66.6% specificity. Our work provides a solid framework upon which to build a future "breathalyzer" test for SARS-CoV-2 infection in children.