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

Stanislas Grassin-Delyle; Camille Roquencourt; Pierre Moine; Gabriel Saffroy; Stanislas Carn; Nicholas Heming; Jérôme Fleuriet; Hélène Salvator; Emmanuel Naline; Louis-Jean Couderc; Philippe Devillier; Etienne A Thévenot; Djillali Annane; Garches COVID-19 Collaborative Group RECORDS Collaborators and Exhalomics® Collaborators

doi:10.1016/j.ebiom.2020.103154

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

EBioMedicine. 2021 Jan:63:103154. doi: 10.1016/j.ebiom.2020.103154. Epub 2020 Dec 4.

Authors

Affiliations

¹ 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.).. Electronic address: stanislas.grassin-delyle@uvsq.fr.
² CEA, LIST, Laboratoire Sciences des Données et de la Décision, Gif-sur-Yvette, France (C.R.).
³ 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.).
⁴ 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.).
⁵ 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.).
⁶ 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.).
⁷ 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.).

Abstract

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 25^th and June 25^th, 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.

Keywords: Breath analysis; COVID-19; Intensive care; Mechanical ventilation; Metabolomics.

MeSH terms

Aged
Area Under Curve
Breath Tests
COVID-19 / pathology*
COVID-19 / virology
Critical Illness
Discriminant Analysis
Female
Humans
Least-Squares Analysis
Male
Metabolomics / methods*
Middle Aged
Pilot Projects
Principal Component Analysis
Prospective Studies
ROC Curve
Respiration, Artificial
Respiratory Distress Syndrome / pathology
SARS-CoV-2 / isolation & purification
Volatile Organic Compounds / analysis*
Volatile Organic Compounds / metabolism

Substances

Volatile Organic Compounds