ABSTRACT
Background: A novel human coronavirus, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), emerged in China in late 2019 and has since claimed more than one million lives. COVID-19 infection is perceived to be seasonally recurrent and a rapid non-invasive biomarker to accurately diagnose patients early-on in their disease course will be necessary to meet the operational demands for COVID-19 control in the coming years.Objective: To evaluate the role of exhaled breath volatile breath biomarkers in identifying patients with suspected or confirmed COVID 19 infection, based on their underlying reverse transcriptase polymerase chain reaction (RT-PCR) status. Methods: We conducted an observational study at Glenfield Hospital, Leicester, United Kingdom, recruiting adult patients with suspected or confirmed COVID19 pneumonia. Breath samples were collected using a standard breath collection bag, modified with appropriate filters to comply with local infection control recommendations and samples were analysed using gas chromatography mass spectrometry (GC-MS).Findings: 81 patients were recruited, of whom 52/81 (64%) have subsequently tested positive for COVID19. A LASSO regression analysis, with the dependent variable as PCR status was run. A set of seven features were extracted that had non-zero regression coefficients in at least 70 out of 100 runs of 10-fold cross validation. Compound identities were confirmed using the Metabolomics Standards Initiative (MSI). These were benzaldehyde, 1-propanol (MSI level 1), 3,6-methylundecane (MSI level 2), camphene and beta-cubebene (MSI level 1 and 2 respectively). Iodobenzene was also extracted, likely of exogenous origin, and an unidentified compound. A logistic regression model was fitted with the dependent variable as PCR status and independent variables as the seven features selected by the LASSO model. Partial Least Squares Discriminant Analysis (PLSDA) and Principal Component Analysis (PCA) were applied to the seven features, with the dependent variable as PCR status. The AUC for the first discriminant function score was 0.836 (95% CI: 0.745-0.928), Sensitivity was 0.68 (95% CI 0.551-0.809), Specificity was 0.857 (95% CI 0.728-0.987), positive predictive value (PPV) was 0.895 (95% CI 0.797-0.992) and negative predictive value (NPV) was 0.6 (95% CI 0.448-0.752). The AUC for the first PCA was 0.799 (95% CI: 0.698-0.900), Sensitivity was 0.7 (95% CI 0.573-0.827), Specificity was 0.786 (95% CI 0.634-0.938), PPV was 0.854 (95% CI 0.745-0.962) and NPV was 0.595 (95% CI 0.436-0.753).Conclusions: breath analysis has promising combined sensitivity and specificity in detecting COVID19, raising the possibility of mass rapid testing, pending external validation of the identified biomarkers.