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EClinicalMedicine

Title:		Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry - a feasibility study
Author(s):		Ruszkiewicz DM; Sanders D; O'Brien R; Hempel F; Reed MJ; Riepe AC; Bailie K; Brodrick E; Darnley K; Ellerkmann R; Mueller O; Skarysz A; Truss M; Wortelmann T; Yordanov S; Thomas CLP; Schaaf B; Eddleston M;
Address:		"Centre for Analytical Science, Chemistry, School of Science, Loughborough University, LE11 3TU, United Kingdom. G.A.S. Gesellschaft fur analytische Sensorsysteme mbH BioMedizinZentrumDortmund, Dortmund, DE, Germany. Emergency Medicine Research Group Edinburgh (EMERGE), Department of Emergency Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, United Kingdom. Klinikum Dortmund, Beurhausstr. 40, 44137 Dortmund, DE, Germany. Edinburgh Acute Care, Usher Institute of Population Health Sciences and Informatics, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom. IMSPEX Diagnostics Ltd, Ty Menter, Navigation Park, Abercynon, RCT CF45 4SN, United Kingdom. Wellcome Clinical Research Facility, NHS Lothian, Edinburgh EH4 2XU, United Kingdom. Computer Science Department, School of Science, Loughborough University, United Kingdom. Pharmacology, Toxicology & Therapeutics, Centre for Cardiovascular Science, University of Edinburgh, United Kingdom"
Journal Title:		EClinicalMedicine
Year:		2020
Volume:		20201024
Issue:
Page Number:		100609 -
DOI:		10.1016/j.eclinm.2020.100609
ISSN/ISBN:		2589-5370 (Electronic) 2589-5370 (Linking)
Abstract:		"BACKGROUND: There is an urgent need to rapidly distinguish COVID-19 from other respiratory conditions, including influenza, at first-presentation. Point-of-care tests not requiring laboratory- support will speed diagnosis and protect health-care staff. We studied the feasibility of using breath-analysis to distinguish these conditions with near-patient gas chromatography-ion mobility spectrometry (GC-IMS). METHODS: Independent observational prevalence studies at Edinburgh, UK, and Dortmund, Germany, recruited adult patients with possible COVID-19 at hospital presentation. Participants gave a single breath-sample for VOC analysis by GC-IMS. COVID-19 infection was identified by transcription polymerase chain reaction (RT- qPCR) of oral/nasal swabs together with clinical-review. Following correction for environmental contaminants, potential COVID-19 breath-biomarkers were identified by multi-variate analysis and comparison to GC-IMS databases. A COVID-19 breath-score based on the relative abundance of a panel of volatile organic compounds was proposed and tested against the cohort data. FINDINGS: Ninety-eight patients were recruited, of whom 21/33 (63.6%) and 10/65 (15.4%) had COVID-19 in Edinburgh and Dortmund, respectively. Other diagnoses included asthma, COPD, bacterial pneumonia, and cardiac conditions. Multivariate analysis identified aldehydes (ethanal, octanal), ketones (acetone, butanone), and methanol that discriminated COVID-19 from other conditions. An unidentified-feature with significant predictive power for severity/death was isolated in Edinburgh, while heptanal was identified in Dortmund. Differentiation of patients with definite diagnosis (25 and 65) of COVID-19 from non-COVID-19 was possible with 80% and 81.5% accuracy in Edinburgh and Dortmund respectively (sensitivity/specificity 82.4%/75%; area-under-the-receiver- operator-characteristic [AUROC] 0.87 95% CI 0.67 to 1) and Dortmund (sensitivity / specificity 90%/80%; AUROC 0.91 95% CI 0.87 to 1). INTERPRETATION: These two studies independently indicate that patients with COVID-19 can be rapidly distinguished from patients with other conditions at first healthcare contact. The identity of the marker compounds is consistent with COVID-19 derangement of breath-biochemistry by ketosis, gastrointestinal effects, and inflammatory processes. Development and validation of this approach may allow rapid diagnosis of COVID-19 in the coming endemic flu seasons. FUNDING: MR was supported by an NHS Research Scotland Career Researcher Clinician award. DMR was supported by the University of Edinburgh ref COV_29"
Keywords:		Aldehydes Breath-analysis Breath-testing Covid-19 diagnostics Gc-ims Gas chromatography-ion mobility spectrometry Ketones Methanol Multi-variate analysis;
Notes:		"PubMed-not-MEDLINERuszkiewicz, Dorota M Sanders, Daniel O'Brien, Rachel Hempel, Frederik Reed, Matthew J Riepe, Ansgar C Bailie, Kenneth Brodrick, Emma Darnley, Kareen Ellerkmann, Richard Mueller, Oliver Skarysz, Angelika Truss, Michael Wortelmann, Thomas Yordanov, Simeon Thomas, C L Paul Schaaf, Bernhard Eddleston, Michael eng England 2020/11/03 EClinicalMedicine. 2020 Dec; 29:100609. doi: 10.1016/j.eclinm.2020.100609. Epub 2020 Oct 24"