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. [email protected].

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