Background: The COVID-19 pandemic with its worldwide spread, plays an example of viral communicable disease. A rapid, non-invasive diagnostic method is essential to interrupt early infection chains. RT-PCR tests are the current golden standard for COVID- 19 diagnostic, though infeasible for broad population screening due to expense, special kit requirements and prolonged result turnover. Volatile organic compounds analyzed in exhaled breath by GC- IMS offer a promising quick, non- invasive, and practical screening tool. Methods: An experimental, non-randomized controlled study was performed to assess the testability of SARS-CoV2 via exhaled breath using GC-IMS. Patients hospitalized at REGIOMED hospital in Coburg between April and July 2022 were PCR tested for SARS-CoV2 via nasopharyngeal swab, following hospital COVID-19 pandemic policies. Within 24 hours eligible patients (> 18 years) were asked to participate in the study. Exhaled breath was subsequently collected and analyzed using GC-IMS. The collected data were statistically evaluated using IBM SPSS 25. Descriptive statistics, the Mann-Whitney U test, the chi-squared test and Fisher's exact test were applied with p- value set at <0.05. To identify significant VOCs in GC-IMS spectra, software based on cluster analysis followed by multivariate statistical analysis were employed. Results: 89 patients were measured and analyzed in this study. 58 individuals tested positive for SARS- CoV-2 with RT-PCR and a mean CT value of 25.9. No significant differences were found between the groups in terms of age and gender. The GC-IMS analysis of breath revealed 51 Clusters, of which 3 appeared to be relevant for COVID-19. The classification results showed that 76.4% of the original grouped cases were correctly classified, while 75.3% of cross-validated grouped cases were correctly classified. Sensitivity appeared to be 78.9% and specificity 71.9%. Conclusion: The results of this experimental case control study demonstrate that COVID-19, as an example of viral communicable disease, can be detected by GC- IMS through exhaled breath. The measurement of exhaled breath and its analysis by GC- IMS based on VOC composition is non- invasive, fast (<5 min), low- cost, easily performed and readily available test, and offers a promising tool for a point- of care screening or pre-screening method. 49 However, due to the moderate accuracy in this study, further broad-population, experimental studies are required to validate the diagnostic accuracy of exhaled breath analysis by GC-IMS.