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Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry - a feasibility study

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journal contribution
posted on 2020-11-04, 11:59 authored by Dorota Ruszkiewicz, Daniel Sanders, Rachel O'Brien, Frederik Hempel, Matthew Reed, Ansgar Riepe, Kenneth Bailie, Emma Brodrick, Kareen Darnley, Richard Ellerkmann, Oliver Mueller, Angelika Skarysz, Michael Truss, Thomas Wortelmann, Simeon Yordanov, Paul Thomas, Bernhard Schaaf, Michael Eddleston
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.

History

School

  • Science

Department

  • Chemistry

Published in

EClinicalMedicine

Volume

29-30

Publisher

The Lancet. Published by Elsevier Ltd.

Version

  • VoR (Version of Record)

Rights holder

© 2020 The Authors. Published by Elsevier Ltd.

Publisher statement

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Acceptance date

2020-10-09

Publication date

2020-10-24

Copyright date

2020

ISSN

2589-5370

eISSN

2589-5370

Language

  • en

Depositor

Deposit date: 4 November 2020

Article number

100609

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