Abstract
Rapid, high-throughput diagnostic tests are essential to decelerate the spread of the novel coronavirus disease 2019 (COVID-19) pandemic. While RT-PCR tests performed in centralized laboratories remain the gold standard, rapid point-of-care antigen tests might provide faster results. However, they are associated with markedly reduced sensitivity. Bedside breath gas analysis of volatile organic compounds detected by ion mobility spectrometry (IMS) may enable a quick and sensitive point-of-care testing alternative. In this proof-of-concept study, we investigated whether gas analysis by IMS can discriminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from other respiratory viruses in an experimental set-up. Repeated gas analyses of air samples collected from the headspace of virus-infected in vitro cultures were performed for 5 days. A three-step decision tree using the intensities of four spectrometry peaks correlating to unidentified volatile organic compounds allowed the correct classification of SARS-CoV-2, human coronavirus-NL63, and influenza A virus H1N1 without misassignment when the calculation was performed with data 3 days post infection. The forward selection assignment model allowed the identification of SARS-CoV-2 with high sensitivity and specificity, with only one of 231 measurements (0.43%) being misclassified. Thus, volatile organic compound analysis by IMS allows highly accurate differentiation of SARS-CoV-2 from other respiratory viruses in an experimental set-up, supporting further research and evaluation in clinical studies.
Highlights
Rapid, high-throughput diagnostic tests are essential to decelerate the spread of the novel coronavirus disease 2019 (COVID-19) pandemic
The first efforts to detect SARS-CoV-2 by breath gas analysis have been reported[16,17,18,19,20], but further refinement of methods and studies with higher patient numbers are urgently needed. In this proof-of-concept study, we aimed to investigate whether gas analysis by multi-capillary column (MCC)-ion mobility spectrometry (IMS) allows the discrimination of SARS-CoV-2 from other respiratory viruses in an experimental setup
VeroE6 cells were infected with SARS-CoV-2, human coronavirus-NL63, or influenza A virus H1N1 (IAV-H1N1), and MCC-IMS was performed every 12.5 min for 72 h of cultivation
Summary
High-throughput diagnostic tests are essential to decelerate the spread of the novel coronavirus disease 2019 (COVID-19) pandemic. Bedside breath gas analysis of volatile organic compounds detected by ion mobility spectrometry (IMS) may enable a quick and sensitive point-of-care testing alternative. In this proof-of-concept study, we investigated whether gas analysis by IMS can discriminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from other respiratory viruses in an experimental set-up. The short measurement time of about 5–12 min for MCC-IMS is another benefit in contrast to a thermodesorption-based mass spectrometry method for the analysis of VOCs like GC/MSD (gaschromatography coupled mass selective detector), which takes 30–120 min The latter method relies on high-purity helium and liquid nitrogen for the thermodesorption[11]. The first efforts to detect SARS-CoV-2 by breath gas analysis have been reported[16,17,18,19,20], but further refinement of methods and studies with higher patient numbers are urgently needed
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