Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia

Chel Hee Lee; Mohammad M Banoei; Mariam Ansari; Matthew P Cheng; Francois Lamontagne; Donald Griesdale; David E Lasry; Koray Demir; Vinay Dhingra; Karen C Tran; Terry Lee; Kevin Burns; David Sweet; John Marshall; Arthur Slutsky; Srinivas Murthy; Joel Singer; David M Patrick; Todd C Lee; John H Boyd; Keith R Walley; Robert Fowler; Greg Haljan; Donald C Vinh; Alison Mcgeer; David Maslove; Puneet Mann; Kathryn Donohoe; Geraldine Hernandez; Genevieve Rocheleau; Uriel Trahtemberg; Anand Kumar; Ma Lou; Claudia Dos Santos; Andrew Baker; James A Russell; Brent W Winston; *ARBs CORONA I. Investigators

doi:10.1186/s13054-024-04843-0

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia

Crit Care. 2024 Feb 27;28(1):63. doi: 10.1186/s13054-024-04843-0.

Authors

Chel Hee Lee¹, Mohammad M Banoei¹, Mariam Ansari¹, Matthew P Cheng², Francois Lamontagne³, Donald Griesdale⁴, David E Lasry², Koray Demir², Vinay Dhingra⁴, Karen C Tran⁵, Terry Lee⁶, Kevin Burns⁷, David Sweet⁸, John Marshall⁹, Arthur Slutsky¹⁰, Srinivas Murthy¹¹, Joel Singer⁶, David M Patrick¹², Todd C Lee², John H Boyd^{13

14}, Keith R Walley^{13

14}, Robert Fowler¹⁵, Greg Haljan¹⁶, Donald C Vinh², Alison Mcgeer¹⁷, David Maslove¹⁸, Puneet Mann¹⁹, Kathryn Donohoe¹⁹, Geraldine Hernandez¹⁹, Genevieve Rocheleau¹⁹, Uriel Trahtemberg^{20

21

22}, Anand Kumar²³, Ma Lou²³, Claudia Dos Santos²⁴, Andrew Baker²⁵, James A Russell^{13

14}, Brent W Winston²⁶; *ARBs CORONA I. Investigators

Collaborators

*ARBs CORONA I. Investigators:
J A Russell, K R Walley, J Boyd, T Lee, J Singer, D Sweet, K Tran, S Reynolds, G Haljan, M Cheng, D Vinh, T Lee, F Lamontagne, B Winston, O Rewa, J Marshall, A Slutsky, A McGeer, V Sivanantham, R Fowler, D Maslove, S Perez Patrigeon, K D Burns

Affiliations

¹ Department of Critical Care Medicine, University of Calgary, Alberta, Canada.
² Divisions of Infectious Diseases & Medical Microbiology, McGill University Health Center, McGill's Interdisciplinary Initiative in Infection and Immunity, Montreal, PQ, Canada.
³ University of Sherbrooke, Sherbrooke, QC, Canada.
⁴ Critical Care Medicine, Vancouver General Hospital and University of British Columbia, 2775 Laurel St, Vancouver, BC, V5Z 1M9, Canada.
⁵ Division of General Internal Medicine, Vancouver General Hospital and University of British Columbia, 2775 Laurel St, Vancouver, BC, V5Z 1M9, Canada.
⁶ Centre for Health Evaluation and Outcome Science (CHEOS), St. Paul's Hospital and University of British Columbia, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
⁷ Department of Medicine, Division of Nephrology, Ottawa Hospital Research Institute, and University of Ottawa, 1967 Riverside Dr., Rm. 535, Ottawa, ON, K1H 7W9, Canada.
⁸ Critical Care Medicine and Emergency Medicine, Vancouver General Hospital and University of British Columbia, 2775 Laurel St, Vancouver, BC, V5Z 1M9, Canada.
⁹ Department of Surgery, St. Michael's Hospital and University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
¹⁰ Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
¹¹ British Columbia Children's Hospital, University of British Columbia, 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada.
¹² British Columbia Centre for Disease Control (BCCDC) and School of Population and Public Health, University of British Columbia, 655 West 12th Avenue, Vancouver, BC, V5Z 4R4, Canada.
¹³ Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁴ Division of Critical Care Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁵ Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
¹⁶ Department of Medicine and Critical Care Medicine, Surrey Memorial Hospital, 13750 96th Avenue, Surrey, BC, V3V 1Z2, Canada.
¹⁷ Mt. Sinai Hospital and University of Toronto, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
¹⁸ Department of Critical Care, Kingston General Hospital and Queen's University, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada.
¹⁹ Black Tusk, Vancouver, BC, Canada.
²⁰ Department of Critical Care, Galilee Medical Center, Nahariya, Israel.
²¹ Bar Ilan University, Ramat Gan, Israel.
²² Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.
²³ Departments of Medicine and Medical Microbiology, University of Manitoba, Winnipeg, Canada.
²⁴ Department of Medicine and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada.
²⁵ Departments of Critical Care and Anesthesia, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
²⁶ Departments of Critical Care Medicine, Medicine and Biochemistry and Molecular Biology, University of Calgary, Health Research Innovation Center (HRIC), Room 4C64, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada. bwinston@ucalgary.ca.

Abstract

Rationale: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair.

Objective: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis.

Methods: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms.

Results: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms.

Conclusion: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

Keywords: Acute respiratory distress syndrome; H1N1; Metabolomics; Pneumonia; SARS-CoV-2.

MeSH terms

COVID-19* / complications
Chromatography, Liquid
Humans
Influenza A Virus, H1N1 Subtype*
Influenza, Human* / complications
Influenza, Human* / therapy
Lysine
Pneumonia, Bacterial*
Pyruvates
Respiratory Distress Syndrome* / complications
Respiratory Distress Syndrome* / therapy
Tandem Mass Spectrometry

Substances

Lysine
Pyruvates