A Comprehensive Meta-Analysis and Systematic Review of Breath Analysis in Detection of COVID-19 through Volatile Organic Compounds

Background The COVID-19 pandemic had profound global impacts on daily lives, economic stability, and healthcare systems. Diagnosis of COVID-19 infection via RT-PCR was crucial in reducing spread of disease and informing treatment management. While RT-PCR is a key diagnostic test, there is room for improvement in the development of diagnostic criteria. Identification of volatile organic compounds (VOCs) in exhaled breath provides a fast, reliable, and economically favorable alternative for disease detection. Methods This meta-analysis analyzed the diagnostic performance of VOC-based breath analysis in detection of COVID-19 infection. A systematic review of twenty-nine papers using the grading criteria from Newcastle-Ottawa Scale (NOS) and PRISMA guidelines was conducted. Results The cumulative results showed a sensitivity of 0.92 (95% CI, 90%-95%) and a specificity of 0.90 (95% CI 87%-93%). Subgroup analysis by variant demonstrated strong sensitivity to the original strain compared to the Omicron and Delta variant in detection of SARS-CoV-2 infection. An additional subgroup analysis of detection methods showed eNose technology had the highest sensitivity when compared to GC-MS, GC-IMS, and high sensitivity-MS. Conclusion Overall, these results support the use of breath analysis as a new detection method of COVID-19 infection.