Profiling of Exhaled Volatile Organics in the Screening Scenario of a COVID-19 Test Center

Due to their immediate exhalation after generation at the cellular level exhaled volatile organics (VOCs) may provide real-time information on pathophysiological mechanisms and host response to infections. We conducted real-time mass-spectrometry based consecutive breath profiling in 708 subjects under conditions of a realistic screening scenario in a COVID-19 test center. Recruited subjects were grouped for further comparisons, based on PCR confirmed infection status (infected by SARS-CoV-2 or other respiratory pathogens and healthy), RT-qPCR cycle threshold (Ct) values and presence or absence of flu like symptoms. Exhaled VOC profiles of SARS-CoV-2 positive cases (n=36) differed from healthy (n=256) and other respiratory infections (n=416). VOC concentrations also differed between symptomatic and asymptomatic subjects. Unlike previous studies, we observed suppressions of most breath markers in COVID-19. Under-expressions of butyric acid was found as SARS-CoV-2 infection characteristic. Irrespective of tracible disease symptoms, dimethyl sulfide decreased with increasing viral loads. Other VOCs linked to immune host response were over-expressed in cases with respiratory pathogens other than SARS-CoV-2. Alike recent metagenomic and bio-chemical reports, breath profiles of exhaled VOCs mirror interactions of virus with hosts’ cellular metabolism, immune homeostasis of the systemic microbiome. Decreased exhalations of specific volatiles can be attributed to suppressive effects of SARS-CoV-2 onto gut- or pulmonary microbial metabolism. Thus, breath analysis holds potential for monitoring SARS-CoV-2 infections rather than for primary diagnosis. Breath VOC profiling offers knowledge on host-virus cross-talk beyond conventional understanding of microbiology and non-invasive monitoring of pathobiological events linked to viral entry and disease manifestation.Funding Information:he study was supported by European Union’s Regional Development Fund (EFRE) (J.K. Schubert and W. Miekisch), H2020-EU-ITN-IMPACT Marie Skłodowska-Curie grant (IMPACT. 674911) (J.K. Schubert and W. Miekisch) and the Inno-INDIGO-NCDs-CAPomics Project (BMBF 01DQ16010) (J.K. Schubert and W. Miekisch). Conflict of Interests: The authors declare no competing interests.Ethical Approval: Ethical approval by the institutional ethics committee (IEC) of Rostock University Medical Centre (approval No: A 2020 0085, date of permission 17th April 2020) and signed informed consent obtained. The single centre prospective observational study was carried out in accordance with the amended ‘Declaration of Helsinki’ guidelines.