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 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.

Scent dog identification of SARS-CoV-2 infections, similar across different body fluids

“…This was however not within the scope of the current study. The laboratory identification of the specific VOC pattern is still in its infancy, but some current studies under review and also a peer-reviewed one showed SARS-CoV-2 specific biomarkers in breath samples detectable by gas chromatography-ion mobility spectrometry 27,28 , which also support our hypothesis. Scent dogs should be considered an addition to the gold standard RT-PCR, for rapid testing in situations where great numbers of people from different origins come together.…”

Highly selective gas sensing enabled by filters

“…can also be used to monitor naturally 323 occurring methanol during liquor distillation (e.g., fruit spirit or whisky), detect methanol in the breath of methanol poisoning victims to initiate immediate and appropriate treatment with better chance of recovery, 324 and detect the presence of methanol in sanitizers, responsible for 4700 deaths in Iran 325 and USA 326 during the recent COVID-19 pandemic. Even screening for COVID-19 by a quick breath test might be possible after recent research 327 suggested methanol as one of the tentative breath markers of the disease. Or, a sensor enabled by a catalytic filter can selectively detect acetone in the breath.…”

Detecting SARS-CoV-2 in the Breath of COVID-19 Patients

“…During 2020, the human race suffered from the COVID-19 pandemic (1-6) but fortunately learned the importance of controlling transmission through air (7)(8)(9)(10)(11). As a main source of aerosol spread of respiratory viruses, exhaled breath of patients has been confirmed as a potential risk using various methods of sampling and subsequent testing (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Several groups have reported SARS-CoV-2 positivity in samples of exhaled breath condensate (EBC) (21)(22)(23)(24)(25), and based on Ct values, Ma et al further showed that EBC-positive COVID-19 patients exhaled millions of SARS-CoV-2 RNA copies per hour (23).…”

“…Several groups have reported SARS-CoV-2 positivity in samples of exhaled breath condensate (EBC) (21)(22)(23)(24)(25), and based on Ct values, Ma et al further showed that EBC-positive COVID-19 patients exhaled millions of SARS-CoV-2 RNA copies per hour (23). Standard diagnosis of viruses based on swabs or serum has been rapidly developed (17,(26)(27)(28)(29), while auxiliary methods, such as trace biomarkers of COVID-19 in exhalations, have also been explored (18)(19)(20). Nevertheless, there is an urgent need for novel methods to detect SARS-CoV-2 in the transmission path.…”