Development of a new point-of-care COVID-19 screening using exhaled-breath volatilome analysis.

BACKGROUND: The inability to rapidly detect SARS-CoV-2 infection during the COVID-19 pandemic inspired strict lockdown policies, resulting in unprecedented economic adversity and clogging the health care sys-tem. As countries’ fears for second and third wave outbreaks are becoming reality, there is an urgent need for globally available, easy-to-perform, non-invasive, on-the-spot diagnostic tests to detect SARS-CoV-2 and to predict COVID-19 disease progression.

KEY HYPOTHESIS: SARS-CoV-2 infection and COVID-19 disease alters patients’ exhaled-breath metabolite volatile organic compound (VOC) composition. We aim to identify diagnostic and predictive VOC biomarker signatures for COVID-19 disease severity via exhaled-breath analysis.

EXPERIMENTAL PLAN: In this collaborative pilot study, the Belgian COVID-19 national reference center (department of laboratory medicine, UZ Leuven, headed by Marc Van Ranst (MVR)) and the Peter Carmeliet (PCA) laboratory (KU Leuven, VIB) combine expertise to correlate exhaled-breath VOC profiles from COVID-19 suspected patients presenting at the UZ Leuven emergency unit with gold standard diag-nostic tests (PCR, CT-scan, seroconversion) and clinical progression (respiratory distress, mortality). We will validate our VOC signatures in large independent patient cohorts in follow-up studies. Sample collection can start soon, while expertise and experience are available.

OUTCOME: Exhaled-breath VOC signatures to detect SARS-CoV-2 infection, to predict COVID-19 disease progression, and to monitor active disease.

FUTURE PERSPECTIVES: Our short-term ambition is to develop an exhaled air-based metabolomics assay, using mass spectrometry and artificial intelligence (machine learning), to define a diagnostic and predictive me-tabolite signature of COVID-19 disease severity. Our long-term ambition is to develop a globally available, easy-to-use, on-the-spot exhaled air-based metabolite signature detection kit (similar as the exhaled air alcohol detection kit). We will seek industrial collaborations to develop point-of-care testing (POCT). Such devices can be used globally to triage patients at hospitals, companies, schools, airports, retirement homes, etc., and effectively reduce the need for national lockdown policies in both developed and developing coun-tries. Similar approaches can be applicable for mutated SARS-CoV-2 or even other Corona viruses. Another advantage of our approach is the analysis of SARS-CoV-2 protein using exhaled-breath condensate.