1. Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry - a feasibility study
- Author
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Simeon Yordanov, Angelika Skarysz, Daniel Sanders, Dorota Ruszkiewicz, C. L. Paul Thomas, Michael Eddleston, Kenneth Bailie, Matthew J. Reed, Rachel O’Brien, Frederik Hempel, Richard Ellerkmann, Oliver Mueller, Emma Brodrick, Bernhard Schaaf, Kareen Darnley, Thomas Wortelmann, Ansgar C Riepe, and Michael Truss
- Subjects
medicine.medical_specialty ,GC-IMS ,Multivariate analysis ,Coronavirus disease 2019 (COVID-19) ,Covid-19 diagnostics ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Breath-analysis ,Internal medicine ,Medicine ,030212 general & internal medicine ,0101 mathematics ,Medical diagnosis ,Royal infirmary ,Asthma ,Aldehydes ,COPD ,Adult patients ,Multi-variate analysis ,business.industry ,Methanol ,010102 general mathematics ,Bacterial pneumonia ,General Medicine ,Ketones ,Institutional review board ,medicine.disease ,Breath gas analysis ,Gas chromatography-ion mobility spectrometry ,Cohort ,Breath-testing ,business ,Research Paper - 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 studies at Edinburgh, UK, and Dortmund, Germany, recruited adult patients with possible Covid-19 at hospital presentation. Participants gave a single breath-sample for volatile organic compounds analysis by GC-IMS. Covid-19 infection was identified by 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 Statement: MR was supported by an NHS Research Scotland Career Researcher Clinician award. DMR was supported by the University of Edinburgh ref COV_29 Declaration of Interests: The authors have nothing to declare. Ethics Approval Statement: Two independent studies were set up in the emergency departments of the Royal Infirmary of Edinburgh (RIE, Institutional Review Board ref RIE, 20/SS/0042), UK, and Klinikum Dortmund (KD, Institutional Review Board ref IfADo 176/2020), Germany.
- Published
- 2020