Metabolomics of exhaled breath in critically ill COVID-19 patients: A pilot study

Stanislas Grassin-Delyle (1, 2) , Camille Roquencourt (3) , Pierre Moine (4, 2) , Gabriel Saffroy (4) , Stanislas Carn (4) , Nicholas Heming (4, 2) , Jérôme Fleuriet (4) , Hélène Salvator (1) , Emmanuel Naline (1) , Louis-Jean Couderc (1) , Philippe Devillier (1) , Etienne Thévenot (5, 6) , Djillali Annane (4, 2)

1 Service de pneumologie [Hôpital Foch]
2 2I - Infection et inflammation
3 LS2D (CEA, LIST) - Laboratoire Sciences des Données et de la Décision (CEA, LIST)
4 Hôpital Raymond Poincaré [AP-HP]
5 SPI - Service de Pharmacologie et Immunoanalyse
6 MTS - Médicaments et Technologies pour la Santé

Background Early diagnosis of coronavirus disease 2019 (COVID-19) is of the utmost importance but remains challenging. The objective of the current study was to characterize exhaled breath from mechanically ventilated adults with COVID-19. Methods In this prospective observational study, we used real-time, online, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of expired air from adults undergoing invasive mechanical ventilation in the intensive care unit due to severe COVID-19 or non-COVID-19 acute respiratory distress syndrome (ARDS). Findings Between March 25th and June 25th, 2020, we included 40 patients with ARDS, of whom 28 had proven COVID-19. In a multivariate analysis, we identified a characteristic breathprint for COVID-19. We could differentiate between COVID-19 and non-COVID-19 ARDS with accuracy of 93% (sensitivity: 90%, specificity: 94%, area under the receiver operating characteristic curve: 0•94-0•98, after cross-validation). The four most prominent volatile compounds in COVID-19 patients were methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal. Interpretation The real-time, non-invasive detection of methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal in exhaled breath may identify ARDS patients with COVID-19.

Mots clés: COVID-19; Intensive care; Mechanical ventilation; Breath analysis; Metabolomics; Statistical analysis; coronavirus; volatile compound; TOF mass spectrometry; mass spectrometry; spectrum analysis; signal processing; multivariate analysis; acute respiratory distress syndrome; real-time; non-invasive detection

Domaines: Traitement du signal et de l'image [eess.SP]; Bio-informatique [q-bio.QM]; Analyse numérique [cs.NA]; Applications [stat.AP]; Maladies infectieuses; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Stanislas Grassin-Delyle, Camille Roquencourt, Pierre Moine, Gabriel Saffroy, Stanislas Carn, et al.. Metabolomics of exhaled breath in critically ill COVID-19 patients: A pilot study. EBioMedicine, 2021, 63, pp.103154. ⟨10.1016/j.ebiom.2020.103154⟩. ⟨cea-03086093⟩