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Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry - a feasibility study.
Ruszkiewicz, 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.
  • Ruszkiewicz DM; Centre for Analytical Science, Chemistry, School of Science, Loughborough University, LE11 3TU, United Kingdom.
  • Sanders D; G.A.S. Gesellschaft für analytische Sensorsysteme mbH BioMedizinZentrumDortmund, Dortmund, DE, Germany.
  • O'Brien R; Emergency Medicine Research Group Edinburgh (EMERGE), Department of Emergency Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, United Kingdom.
  • Hempel F; Klinikum Dortmund, Beurhausstr. 40, 44137 Dortmund, DE, Germany.
  • Reed MJ; Emergency Medicine Research Group Edinburgh (EMERGE), Department of Emergency Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, United Kingdom.
  • Riepe AC; Edinburgh Acute Care, Usher Institute of Population Health Sciences and Informatics, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom.
  • Bailie K; Klinikum Dortmund, Beurhausstr. 40, 44137 Dortmund, DE, Germany.
  • Brodrick E; Emergency Medicine Research Group Edinburgh (EMERGE), Department of Emergency Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, United Kingdom.
  • Darnley K; IMSPEX Diagnostics Ltd, Ty Menter, Navigation Park, Abercynon, RCT CF45 4SN, United Kingdom.
  • Ellerkmann R; Wellcome Clinical Research Facility, NHS Lothian, Edinburgh EH4 2XU, United Kingdom.
  • Mueller O; Klinikum Dortmund, Beurhausstr. 40, 44137 Dortmund, DE, Germany.
  • Skarysz A; Klinikum Dortmund, Beurhausstr. 40, 44137 Dortmund, DE, Germany.
  • Truss M; Computer Science Department, School of Science, Loughborough University, United Kingdom.
  • Wortelmann T; Klinikum Dortmund, Beurhausstr. 40, 44137 Dortmund, DE, Germany.
  • Yordanov S; G.A.S. Gesellschaft für analytische Sensorsysteme mbH BioMedizinZentrumDortmund, Dortmund, DE, Germany.
  • Thomas CLP; Klinikum Dortmund, Beurhausstr. 40, 44137 Dortmund, DE, Germany.
  • Schaaf B; Centre for Analytical Science, Chemistry, School of Science, Loughborough University, LE11 3TU, United Kingdom.
  • Eddleston M; G.A.S. Gesellschaft für analytische Sensorsysteme mbH BioMedizinZentrumDortmund, Dortmund, DE, Germany.
EClinicalMedicine ; 29: 100609, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-893730
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

Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Diagnostic study / Observational study / Prognostic study Topics: Variants Language: English Journal: EClinicalMedicine Year: 2020 Document Type: Article Affiliation country: J.eclinm.2020.100609

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Diagnostic study / Observational study / Prognostic study Topics: Variants Language: English Journal: EClinicalMedicine Year: 2020 Document Type: Article Affiliation country: J.eclinm.2020.100609