Enhanced real-time mass spectrometry breath analysis for the diagnosis of COVID-19

Abstract

BackgroundAlthough rapid screening for and diagnosis of coronavirus disease 2019 (COVID-19) are still urgently needed, most current testing methods are long, costly or poorly specific. The objective of the present study was to determine whether or not artificial-intelligence-enhanced real-time mass spectrometry breath analysis is a reliable, safe, rapid means of screening ambulatory patients for COVID-19.MethodsIn two prospective, open, interventional studies in a single university hospital, we used real-time, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of exhaled breath from adults requiring screening for COVID-19. Artificial intelligence and machine learning techniques were used to build mathematical models based on breath analysis data either alone or combined with patient metadata.ResultsWe obtained breath samples from 173 participants, of whom 67 had proven COVID-19. After using machine learning algorithms to process breath analysis data and further enhancing the model using patient metadata, our method was able to differentiate between COVID-19-positive and -negative participants with a sensitivity of 98%, a specificity of 74%, a negative predictive value of 98%, a positive predictive value of 72% and an area under the receiver operating characteristic curve of 0.961. The predictive performance was similar for asymptomatic, weakly symptomatic and symptomatic participants and was not biased by COVID-19 vaccination status.ConclusionsReal-time, noninvasive, artificial-intelligence-enhanced mass spectrometry breath analysis might be a reliable, safe, rapid, cost-effective, high-throughput method for COVID-19 screening.

Real-time breath metabolomics to assess early response to CFTR modulators in adults with cystic fibrosis: an open-label proof-of-concept study

“…This method allows the untargeted detection of VOCs according to their mass/charge ratio ( m/z ) in the range 15-500 m/z . Instrument settings and data processing methodology were the same as previously reported [15,21].…”

“…A previous study following up 20 F508del-homozygous patients initiating the CFTR modulator dual therapy lumacaftor/ivacaftor reported significant metabolic changes in exhaled breath profiles after three months which persisted at 12 months [13]. Online proton-transfer reaction -mass spectrometry (PTR-MS) is a high-sensitivity, point-of-care technology allowing real-time monitoring of VOCs which has already demonstrated potential for the diagnosis of infectious or cancerous diseases [14][15][16][17][18].…”

ERS International Congress 2023: highlights from the Respiratory Intensive Care Assembly

“…Novel ambulatory diagnosis of COVID-19 was proposed by S. Grassin Delyle (Montigny le Bretonneux, France) using real-time mass spectrometry breath analysis. Volatile organic compound signatures alongside clinical data accurately identified COVID-19 cases with 98% sensitivity and 74% specificity [ 99 ]. S emenova et al .…”

“…Volatile organic compound signatures alongside clinical data accurately identified COVID-19 cases with 98% sensitivity and 74% specificity (99). Anna Semenova (Munich, Germany) presented liquid chromatography of matched serum and broncho alveolar liquid to create disease specific signatures to differentiate COVID-19 from other causes of pneumonia, also showing unique protein profiles on the first day of intubation, that were sustained for 45 days after intubation (100).…”

A benchmark study of data normalisation methods for PTR-TOF-MS exhaled breath metabolomics

“…The datasets from two previous studies were used to benchmark the normalisation methods, both acquired with a PTR quadrupole TOF mass spectrometer (Ionicon Analytik GmbH, Innsbruck, Austria). The first dataset consists of exhaled breath analysis from participants undergoing COVID-19 screening in the emergency department (ED), with data collected over a 12 month period between March 2021 and June 2022 [22]. The second dataset includes analysis of exhaled breath from intubated, ventilated patients with COVID-19-related acute respiratory distress syndrome in the intensive care unit (ICU) between March and June 2020 [23].…”