Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis
Abstract Background Lipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs‐CoV‐2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an...
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Wiley
2023-11-01
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Series: | Clinical and Translational Medicine |
Online Access: | https://doi.org/10.1002/ctm2.1440 |
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author | Hu Meng Arjun Sengupta Emanuela Ricciotti Antonijo Mrčela Divij Mathew Liudmila L. Mazaleuskaya Soumita Ghosh Thomas G. Brooks Alexandra P. Turner Alessa Soares Schanoski Nicholas F. Lahens Ai Wen Tan Ashley Woolfork Greg Grant Katalin Susztak Andrew G. Letizia Stuart C. Sealfon E. John Wherry Krzysztof Laudanski Aalim M. Weljie Nuala J. Meyer Garret A. FitzGerald |
author_facet | Hu Meng Arjun Sengupta Emanuela Ricciotti Antonijo Mrčela Divij Mathew Liudmila L. Mazaleuskaya Soumita Ghosh Thomas G. Brooks Alexandra P. Turner Alessa Soares Schanoski Nicholas F. Lahens Ai Wen Tan Ashley Woolfork Greg Grant Katalin Susztak Andrew G. Letizia Stuart C. Sealfon E. John Wherry Krzysztof Laudanski Aalim M. Weljie Nuala J. Meyer Garret A. FitzGerald |
author_sort | Hu Meng |
collection | DOAJ |
description | Abstract Background Lipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs‐CoV‐2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an intensive care unit (ICU). Methods Mass spectrometry was used to characterise lipids and relate them to proteins, peripheral cell immunotypes and disease severity. Results Circulating phospholipases (sPLA2, cPLA2 (PLA2G4A) and PLA2G2D) were elevated on admission in all ICU groups. Cyclooxygenase, lipoxygenase and epoxygenase products of arachidonic acid (AA) were elevated in all ICU groups compared with controls. sPLA2 predicted severity in COVID‐19 and correlated with TxA2, LTE4 and the isoprostane, iPF2α‐III, while PLA2G2D correlated with LTE4. The elevation in PGD2, like PGI2 and 12‐HETE, exhibited relative specificity for COVID‐19 and correlated with sPLA2 and the interleukin‐13 receptor to drive lymphopenia, a marker of disease severity. Pro‐inflammatory eicosanoids remained correlated with severity in COVID‐19 28 days after admission. Amongst non‐COVID ICU patients, elevations in 5‐ and 15‐HETE and 9‐ and 13‐HODE reflected viral rather than bacterial disease. Linoleic acid (LA) binds directly to SARS‐CoV‐2 and both LA and its di‐HOME products reflected disease severity in COVID‐19. In healthy marines, these lipids rose with seroconversion. Eicosanoids linked variably to the peripheral cellular immune response. PGE2, TxA2 and LTE4 correlated with T cell activation, as did PGD2 with non‐B non‐T cell activation. In COVID‐19, LPS stimulated peripheral blood mononuclear cell PGF2α correlated with memory T cells, dendritic and NK cells while LA and DiHOMEs correlated with exhausted T cells. Three high abundance lipids – ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 – were altered specifically in COVID. LPC‐O‐16:0 was strongly correlated with T helper follicular cell activation and all three negatively correlated with multi‐omic inflammatory pathways and disease severity. Conclusions A broad based lipidomic storm is a predictor of poor prognosis in ARDS. Alterations in sPLA2, PGD2 and 12‐HETE and the high abundance lipids, ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 exhibit relative specificity for COVID‐19 amongst such patients and correlate with the inflammatory response to link to disease severity. |
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institution | Directory Open Access Journal |
issn | 2001-1326 |
language | English |
last_indexed | 2024-03-09T14:11:51Z |
publishDate | 2023-11-01 |
publisher | Wiley |
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series | Clinical and Translational Medicine |
spelling | doaj.art-810742408e2d4ead95afe8bcbe4b3a812023-11-29T06:48:31ZengWileyClinical and Translational Medicine2001-13262023-11-011311n/an/a10.1002/ctm2.1440Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsisHu Meng0Arjun Sengupta1Emanuela Ricciotti2Antonijo Mrčela3Divij Mathew4Liudmila L. Mazaleuskaya5Soumita Ghosh6Thomas G. Brooks7Alexandra P. Turner8Alessa Soares Schanoski9Nicholas F. Lahens10Ai Wen Tan11Ashley Woolfork12Greg Grant13Katalin Susztak14Andrew G. Letizia15Stuart C. Sealfon16E. John Wherry17Krzysztof Laudanski18Aalim M. Weljie19Nuala J. Meyer20Garret A. FitzGerald21Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USADepartment of Systems Pharmacology and Translational Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USADepartment of Systems Pharmacology and Translational Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USADepartment of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USADepartment of Neurology Icahn School of Medicine at Mount Sinai New York New York USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USADepartment of Systems Pharmacology and Translational Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USADepartment of Systems Pharmacology and Translational Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USADepartment of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USANaval Medical Research Center Silver Spring Maryland USADepartment of Neurology Icahn School of Medicine at Mount Sinai New York New York USADepartment of Systems Pharmacology and Translational Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USADepartment of Anesthesiology and Critical Care Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAInstitute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USAAbstract Background Lipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs‐CoV‐2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an intensive care unit (ICU). Methods Mass spectrometry was used to characterise lipids and relate them to proteins, peripheral cell immunotypes and disease severity. Results Circulating phospholipases (sPLA2, cPLA2 (PLA2G4A) and PLA2G2D) were elevated on admission in all ICU groups. Cyclooxygenase, lipoxygenase and epoxygenase products of arachidonic acid (AA) were elevated in all ICU groups compared with controls. sPLA2 predicted severity in COVID‐19 and correlated with TxA2, LTE4 and the isoprostane, iPF2α‐III, while PLA2G2D correlated with LTE4. The elevation in PGD2, like PGI2 and 12‐HETE, exhibited relative specificity for COVID‐19 and correlated with sPLA2 and the interleukin‐13 receptor to drive lymphopenia, a marker of disease severity. Pro‐inflammatory eicosanoids remained correlated with severity in COVID‐19 28 days after admission. Amongst non‐COVID ICU patients, elevations in 5‐ and 15‐HETE and 9‐ and 13‐HODE reflected viral rather than bacterial disease. Linoleic acid (LA) binds directly to SARS‐CoV‐2 and both LA and its di‐HOME products reflected disease severity in COVID‐19. In healthy marines, these lipids rose with seroconversion. Eicosanoids linked variably to the peripheral cellular immune response. PGE2, TxA2 and LTE4 correlated with T cell activation, as did PGD2 with non‐B non‐T cell activation. In COVID‐19, LPS stimulated peripheral blood mononuclear cell PGF2α correlated with memory T cells, dendritic and NK cells while LA and DiHOMEs correlated with exhausted T cells. Three high abundance lipids – ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 – were altered specifically in COVID. LPC‐O‐16:0 was strongly correlated with T helper follicular cell activation and all three negatively correlated with multi‐omic inflammatory pathways and disease severity. Conclusions A broad based lipidomic storm is a predictor of poor prognosis in ARDS. Alterations in sPLA2, PGD2 and 12‐HETE and the high abundance lipids, ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 exhibit relative specificity for COVID‐19 amongst such patients and correlate with the inflammatory response to link to disease severity.https://doi.org/10.1002/ctm2.1440 |
spellingShingle | Hu Meng Arjun Sengupta Emanuela Ricciotti Antonijo Mrčela Divij Mathew Liudmila L. Mazaleuskaya Soumita Ghosh Thomas G. Brooks Alexandra P. Turner Alessa Soares Schanoski Nicholas F. Lahens Ai Wen Tan Ashley Woolfork Greg Grant Katalin Susztak Andrew G. Letizia Stuart C. Sealfon E. John Wherry Krzysztof Laudanski Aalim M. Weljie Nuala J. Meyer Garret A. FitzGerald Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis Clinical and Translational Medicine |
title | Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis |
title_full | Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis |
title_fullStr | Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis |
title_full_unstemmed | Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis |
title_short | Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis |
title_sort | deep phenotyping of the lipidomic response in covid 19 and non covid 19 sepsis |
url | https://doi.org/10.1002/ctm2.1440 |
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