Diagnosis of COVID-19 by Analysis of Breath with Gas Chromatography-Ion Mobility Spectrometry: A Feasibility Study

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 breathsample 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.

Reproducible breath metabolite changes in children with SARS-CoV-2 infection

“…Our studies are also in agreement with recent studies by Ruszkiewicz et al (19), which found that the breath abundance of two aldehydes (octanal and heptanal) were increased in patients diagnosed with COVID-19 compared to those with other acute respiratory illnesses (e.g. COPD and pneumonia).…”

Volatile Organic Compounds in Exhaled Breath as Fingerprints of Lung Cancer, Asthma and COPD

“…That no vacuum system is required dramatically reduces the size and power requirements. Together with its ease of use and robustness, IMS, and particularly GC-IMS, is extremely suitable for use in clinical environments at the point of care [ 100 , 101 , 102 , 103 , 104 ]. The most common types are the classical IMS, a-IMS (aspiration IMS), FAIMS (Field Asymmetric wave IMS) and DMS (differential mobility spectrometry).…”

Changes to the sebum lipidome upon COVID-19 infection observed via rapid sampling from the skin

“…Approaches that measure the indirect effect of the virus on the host (as opposed to direct measurement of the virus itself) may offer a complementary solution in clinical or mass testing settings; for example, one feasibility study has recently identified derangement of breath biochemistry in COVID-19 patients [6] . As the coronavirus requires lipids for reproduction, COVID-19 can be expected to disrupt the lipidome [7] .…”