Ann Arbor, MI—Could breath analysis assays someday replace the boxes of swab COVID-19 tests on pharmacy shelves?

The answer, according to a new study, is quite complicated. University of Michigan researchers sought to determine if volatile organic compounds (VOCs) in exhaled breath could provide diagnostic information on COVID-19 disease and SARS-CoV-2 variants.

It turns out that the constant new variants might be the problem. In the original diagnostic study with 167 participants, four VOC biomarkers had the ability to distinguish between the Delta variant of SARS-CoV-2, as well as other variants occurring in 2021, and non–COVID-19 illness. The emergence of the Omicron variant in 2022, however, required a different set of VOCs to distinguish between the Omicron variant and non–COVID-19 illness, according to the report in JAMA Network Open.

“These findings demonstrate the ability of breath analysis to distinguish between COVID-19 and non–COVID-19 illness, but they also reveal the significant variations in the breath profile among patients with COVID-19 as new SARS-CoV-2 variants emerge,” the researchers advise.

Background information in the article points out that breath analysis has been explored as a noninvasive means to detect COVID-19. In this diagnostic study, participants were patients who had both positive and negative test results for COVID-19 using reverse transcriptase polymerase chain reaction. They were patients enrolled through intensive care units and the emergency department at the University of Michigan Health System. The study team analyzed patient breath with portable gas chromatography between April 2021 and May 2022, which spanned the period when Omicron overtook Delta as the primary variant.

Ultimately, 205 breath samples from 167 adult patients were analyzed. The 77 patients who had COVID-19 had a mean age of 58.5 years and were mostly male, 58.2%, and white. Of the 91 patients who had non-COVID illness, the median age was 54.3 years, most were female, 52.7%, and 83.5% were white.

“Several patients were analyzed over multiple days,” the authors explain. “Among 94 positive samples, 41 samples were from patients in 2021 infected with the Delta or other variants, and 53 samples were from patients in 2022 infected with the Omicron variant, based on the State of Michigan and U.S. Centers for Disease Control and Prevention surveillance data.”

The original four VOC biomarkers were found to be very accurate, 94.7%, in distinguishing between COVID-19 (Delta and other 2021 variants) and non–COVID-19 illness. “However, accuracy dropped substantially to 82.1% when these biomarkers were applied to the Omicron variant,” the researchers point out. “Four new VOC biomarkers were found to distinguish the Omicron variant and non–COVID-19 illness (accuracy, 90.9%). Breath analysis distinguished Omicron from the earlier variants with an accuracy of 91.5% and COVID-19 (all SARS-CoV-2 variants) vs. non–COVID-19 illness with 90.2% accuracy.”

The study concludes that breath analysis is promising for COVID-19 detection but adds, “However, similar to rapid antigen testing, the emergence of new variants poses diagnostic challenges. The results of this study warrant additional evaluation on how to overcome these challenges to use breath analysis to improve the diagnosis and care of patients.”

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