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.

A method for the identification of COVID-19 biomarkers in human breath using Proton Transfer Reaction Time-of-Flight Mass Spectrometry

“…Aldehydes are derived, along with hydrocarbons, from lipid peroxidation and inflammatory processes and have been reported widely in a range of respiratory conditions. Ruszkiewicz and colleagues [16] have also found aldehydes (ethanal, octanal, propanal, heptanal etc.) signals to be elevated in patients with COVID-19 infection.…”

“…Acetaldehyde which has been identified in adults [16] to be increased is not discussed in the children's study [31] . We see it as a primary discriminator in the older population with average double increases for people of over age 55, while the younger population showed less of an increase.…”

“…Multiple studies presented the use of gas chromatography-ion mobility spectrometry (GC-IMS) for the breath analysis [ [14] , [15] , [16] , [17] ]. Ruszkiewicz and colleagues [16] presented a study in which ninety patients from Edinburgh, UK (65 patients, 10 positive COVID-19 cases) and Dortmund, Germany (25 patients, 17 positive COVID-19 cases) were tested. The non-COVID -19 cases were suffering from other respiratory diseases, such as asthma, COPD, and bacterial pneumonia or cardiac diseases.…”

Rapid non-invasive detection of Influenza-A-infection by multicapillary column coupled ion mobility spectrometry

“…In two recent studies posted as preprints MCC-IMS could also identify SARS-CoV-2 infections in breath. 18,19 As MCC-IMS is fast, non-invasive and ressource-saving it could be a breakthrough for SARS-CoV-2 mass screening for travellers and huge cultural events. Hence, we are urgently recommending to spur the further development of this new method.…”

An update on novel approaches for diagnosis and treatment of SARS-CoV-2 infection

“…Various MS-based techniques are used to develop breath analyzer devices that can distinguish suspected COVID-19 patients based on the panel of volatile compounds in their breath as per a survey by the International Federation of Clinical Chemistry (IFCC), August 2020 [48]. A group of researchers in Germany and UK developed a method to detect COVID-19 patients by the analysis of breath using gas chromatography-ion mobility spectrometry (GC-IMS) with the accuracy of 80% [49]. It is suggested that a biomarker panel of volatile organic compounds (e.g., ethanal, octanal, acetone, butanone, methanol, heptanal) provides the basis of a COVID-19 rule-in/rule-out breath-test.…”