Virus-induced breath biomarkers: A new perspective to study the metabolic responses of COVID-19 vaccinees

Coronavirus disease 2019 (COVID-19) vaccines can protect people from the infection; however, the action mechanism of vaccine-mediated metabolism remains unclear. Herein, we performed breath tests in COVID-19 vaccinees that revealed metabolic reprogramming induced by protective immune responses. In total, 204 breath samples were obtained from COVID-19 vaccinees and non-vaccinated controls, wherein numerous volatile organic compounds (VOCs) were detected by comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry system. Subsequently, 12 VOCs were selected as biomarkers to construct a signature panel using alveolar gradients and machine learning-based procedure. The signature panel could distinguish vaccinees from control group with a high prediction performance (AUC, 0.9953; accuracy, 94.42%). The metabolic pathways of these biomarkers indicated that the host-pathogen interactions enhanced enzymatic activity and microbial metabolism in the liver, lung, and gut, potentially constituting the dominant action mechanism of vaccine-driven metabolic regulation. Thus, our findings of this study highlight the potential of measuring exhaled VOCs as rapid, non-invasive biomarkers of viral infections. Furthermore, breathomics appears as an alternative for safety evaluation of biological agents and disease diagnosis.