Ruling out SARS-CoV-2 infection using exhaled breath analysis by electronic nose in a public health setting

Abstract

Background: Rapid and accurate detection of SARS-CoV-2 infected individuals is crucial for taking timely measures and minimizing the risk of further SARS-CoV-2 spread. We aimed to assess the accuracy of exhaled breath analysis by electronic nose (eNose) for the discrimination between individuals with and without a SARS-CoV-2 infection. Methods: This was a prospective real-world study of individuals presenting to public test facility for SARS-CoV-2 detection by molecular amplification tests (TMA or RT-PCR). After sampling of a combined throat/nasopharyngeal swab, breath profiles were obtained using a cloud-connected eNose. Data-analysis involved advanced signal processing and statistics based on independent t-tests followed by linear discriminant and ROC analysis. Data from the training set were tested in a validation, a replication and an asymptomatic set. Findings: For the analysis 4510 individuals were available. In the training set (35 individuals with; 869 without SARS-CoV-2), the eNose sensors were combined into a composite biomarker with a ROC-AUC of 0.947 (CI:0.928-0.967). These results were confirmed in the validation set (0.957; CI:0.942-0.971, n=904) and externally validated in the replication set (0.937; CI:0.926-0.947, n=1948) and the asymptomatic set (0.909; CI:0.879-0.938, n=754). Selecting a cut-off value of 0.30 in the training set resulted in a sensitivity/specificity of 100/78, >99/84, 98/82% in the validation, replication and asymptomatic set, respectively. Interpretation: eNose represents a quick and non-invasive method to reliably rule out SARS-CoV-2 infection in public health test facilities and can be used as a screening test to define who needs an additional confirmation test. Funding: Ministry of Health, Welfare and Sport

Use of emerging testing technologies and approaches for SARS-CoV-2: review of literature and global experience in an Australian context

“…Several countries are at various stages of large clinical evaluations of instruments for breath detection of SARS-CoV-2 infection: examples include GeNose, BreathPass, SpiroNose, Brethonix. 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 Detection technologies employed include gas chromatography, different forms of mass spectrometry, and nanosensors to either detect volatile organic compounds or directly detect the virus. 91 There is a paucity of peer-reviewed literature evaluating large-scale clinical performance of the various assays.…”

“…92 However, another Dutch assay was found to have lower specificity of 82% when tested on asymptomatic persons and not long after it was launched its use was halted by Amsterdam’s Public Health Service after a concern about sensitivity. 93 , 94 Assays with good performance would have the potential to rapidly screen large populations as these assays screen individuals within minutes, but assays with high specificity would be more useful in low-prevalence settings such as Australia.…”

The potential of volatile organic compounds-based breath analysis for COVID-19 screening: a systematic review & meta-analysis.

“…Six articles were included with a total of 4,093 participants. Patients’ recruited in the studies are individuals with suggestive symptoms of COVID-19 ( Wintjens et al, 2020 , Grassin-Delyle et al, 2021 , Ruszkiewicz et al, 2020 , de et al, 2021 ); acute respiratory distress syndrome (ARDS) patients requiring mechanical ventilation ( Grassin-Delyle et al, 2021 ); COVID-19 patients confirmed with RT-PCR ( Berna et al, 2021 , Shan et al, 2020 ), computed tomography (CT) and laboratory (antibody test) ( Shan et al, 2020 ). The study participants were then grouped into two based on their COVID-19 status (positive or negative).…”

“…Three studies ( Ruszkiewicz et al, 2020 , de et al, 2021 , Shan et al, 2020 ) classified their subjects into specific sets to provide a thorough diagnostic evaluation. Ruszkiewicz et al (2020) categorized their study participants based on geographic locations ( Ruszkiewicz et al, 2020 ).…”

Recent Advances in Novel Lateral Flow Technologies for Detection of COVID-19

“…Currently available diagnostic techniques for COVID-19 are based on the detection of the viral gene, antigen, or human antibodies (serological test) and human metabolites [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Among these techniques, the detection of viral RNA sequences by reverse transcription polymerase chain reaction (RT-PCR), reverse transcription loop-mediated isothermal amplification (RT-LAMP), and reverse transcription quantitative polymerase chain reaction (RT-qPCR) have been the most reliable methods.…”