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Passing the Sniff Test: CHOP Researchers Identify SARS-CoV-2 Breath Biomarkers in Children

Researchers at Children’s Hospital of Philadelphia (CHOP) have identified six biomarkers in the breath of children infected with SARS-CoV-2 that could potentially be used to screen for the virus using a breathalyzer. The findings, which were recently published in ACS Infectious Diseases, could lead to the development of a tool to screen children quickly and easily for SARS-CoV-2 infection.

“The COVID-19 pandemic continues to disrupt daily life, even amidst an ongoing international vaccination effort, so having fast and accurate diagnostic tools will be extremely useful as we seek to reduce the spread of the virus,” said Audrey R. Odom John, MD, PhD, Chief of the Division of Pediatric Infectious Diseases at Children’s Hospital of Philadelphia and senior author of the study. “Our study shows that breath biomarkers could be a useful tool in screening for the SARS-CoV-2 virus. Given the cost, discomfort, and false-negative results associated with current testing methods, a breathalyzer test may provide an inexpensive, noninvasive, rapid, and highly sensitive alternative for screening of large numbers of people, like at airports, large indoor events, or even school settings.”

Currently, COVID-19 is diagnosed through a nasal swab test, either using RT-PCR to scan for specific nucleic acids or a so-called “rapid antigen” test. However, the former method is slow, and the latter is prone to false-negative results. Prior studies at Penn Vet have shown that dogs can detect volatile organic compounds (VOCs) that distinguish COVID-19 from negative controls, and other researchers have developed a sensor array to detect COVID-19-related VOCs in adults.

In their study, the CHOP researchers used 2D gas chromatography and time-of-flight mass spectrometry to compare breath samples from 15 children with SARS-CoV-2 and 10 children who tested negative. In analyzing 84 VOCs in the breath samples, the researchers identified six that were significantly elevated in children with COVID-19, raising the possibility of using those VOCs as COVID-19 biomarkers. Although two of the markers had also been documented as elevated in adults with COVID-19, the other four were unique to children. When the researchers scanned a second cohort of children – 12 with a positive PCR test and 12 with a negative test – the researchers replicated their results from the first group, with the same six biomarkers.

“In our work with Penn Vet, the dogs told us a breath test could work, and now we’ve shown how,” John said. “These findings also stress that for a breathalyzer to be broadly useful, it will need to scan for markers that are present in both children and adults, in order to yield the most accurate results across the population.”

The researchers, who have filed for a patent on their discovery, are now analyzing the VOC profiles of other viruses to ensure that a potential SARS-CoV-2 breathalyzer would be both sensitive and accurate.

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