Metabolomics of exhaled breath in critically ill COVID-19 patients: A pilot study
Stanislas Grassin-Delyle, Ph.D.,
Camille Roquencourt, M.S.,
Pierre Moine, M.D.,
Gabriel Saffroy,
Stanislas Carn,
Nicholas Heming, M.D.,
Jérôme Fleuriet, Ph.D.,
Hélène Salvator, M.D.,
Emmanuel Naline, Ph.D.,
Louis-Jean Couderc, M.D.,
Philippe Devillier, M.D.,
Etienne A. Thévenot, Ph.D.,
Djillali Annane, M.D.
Affiliations
Stanislas Grassin-Delyle, Ph.D.
Hôpital Foch, Exhalomics®, Département des maladies des voies respiratoires, Suresnes, France (S.G.D., H.S., E.N., L-J.C., P.D.); Université Paris-Saclay, UVSQ, INSERM, Infection et inflammation, Montigny le Bretonneux, France (S.G.D., P.M., N.H., D.A.); FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis) (S.G.D., H.S., E.N., L-J.C., P.D., E.T., D.A.).; Corresponding author.
Camille Roquencourt, M.S.
CEA, LIST, Laboratoire Sciences des Données et de la Décision, Gif-sur-Yvette, France (C.R.)
Pierre Moine, M.D.
Université Paris-Saclay, UVSQ, INSERM, Infection et inflammation, Montigny le Bretonneux, France (S.G.D., P.M., N.H., D.A.); Intensive Care Unit, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris, Garches, France (P.M., G.S., S.C., N.H., J.F., D.A.)
Gabriel Saffroy
Intensive Care Unit, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris, Garches, France (P.M., G.S., S.C., N.H., J.F., D.A.)
Stanislas Carn
Intensive Care Unit, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris, Garches, France (P.M., G.S., S.C., N.H., J.F., D.A.)
Nicholas Heming, M.D.
Université Paris-Saclay, UVSQ, INSERM, Infection et inflammation, Montigny le Bretonneux, France (S.G.D., P.M., N.H., D.A.); Intensive Care Unit, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris, Garches, France (P.M., G.S., S.C., N.H., J.F., D.A.)
Jérôme Fleuriet, Ph.D.
Intensive Care Unit, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris, Garches, France (P.M., G.S., S.C., N.H., J.F., D.A.)
Hélène Salvator, M.D.
Hôpital Foch, Exhalomics®, Département des maladies des voies respiratoires, Suresnes, France (S.G.D., H.S., E.N., L-J.C., P.D.); FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis) (S.G.D., H.S., E.N., L-J.C., P.D., E.T., D.A.).
Emmanuel Naline, Ph.D.
Hôpital Foch, Exhalomics®, Département des maladies des voies respiratoires, Suresnes, France (S.G.D., H.S., E.N., L-J.C., P.D.); FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis) (S.G.D., H.S., E.N., L-J.C., P.D., E.T., D.A.).
Louis-Jean Couderc, M.D.
Hôpital Foch, Exhalomics®, Département des maladies des voies respiratoires, Suresnes, France (S.G.D., H.S., E.N., L-J.C., P.D.); FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis) (S.G.D., H.S., E.N., L-J.C., P.D., E.T., D.A.).
Philippe Devillier, M.D.
Hôpital Foch, Exhalomics®, Département des maladies des voies respiratoires, Suresnes, France (S.G.D., H.S., E.N., L-J.C., P.D.); FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis) (S.G.D., H.S., E.N., L-J.C., P.D., E.T., D.A.).
Etienne A. Thévenot, Ph.D.
Département Médicaments et Technologies pour la Santé (DMTS), Université Paris-Saclay, CEA, INRAE, MetaboHUB, Gif-sur-Yvette, France (E.T.); FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis) (S.G.D., H.S., E.N., L-J.C., P.D., E.T., D.A.).
Djillali Annane, M.D.
Université Paris-Saclay, UVSQ, INSERM, Infection et inflammation, Montigny le Bretonneux, France (S.G.D., P.M., N.H., D.A.); Intensive Care Unit, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris, Garches, France (P.M., G.S., S.C., N.H., J.F., D.A.); FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis) (S.G.D., H.S., E.N., L-J.C., P.D., E.T., D.A.).
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. Funding: The study was funded by Agence Nationale de la Recherche (SoftwAiR, ANR-18-CE45-0017 and RHU4 RECORDS, Programme d'Investissements d'Avenir, ANR-18-RHUS-0004), Région Île de France (SESAME 2016), and Fondation Foch.
