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Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis

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, View ORCID ProfileStuart C. Sealfon, E. John Wherry, Krzysztof Laudanski, Aalim M. Weljie, Nuala B. Meyer, Garret A. FitzGerald
doi: https://doi.org/10.1101/2023.06.02.543298
Hu Meng
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Arjun Sengupta
2Dept of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Emanuela Ricciotti
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
2Dept of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Antonijo Mrčela
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Divij Mathew
2Dept of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
7Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Liudmila L. Mazaleuskaya
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Soumita Ghosh
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Thomas G. Brooks
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Alexandra P. Turner
3Dept of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Alessa Soares Schanoski
4Dept of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
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Nicholas F. Lahens
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Ai Wen Tan
2Dept of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Ashley Woolfork
2Dept of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Greg Grant
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
5Dept. of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Katalin Susztak
3Dept of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Andrew G. Letizia
6Naval Medical Research Center, Silver Spring, MD, USA and U.S. Naval Medical Research Unit TWO, Singapore, Singapore
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Stuart C. Sealfon
4Dept of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
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  • ORCID record for Stuart C. Sealfon
E. John Wherry
2Dept of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
7Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Krzysztof Laudanski
8Dept of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Aalim M. Weljie
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
2Dept of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Nuala B. Meyer
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
3Dept of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Garret A. FitzGerald
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
2Dept of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
3Dept of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Abstract

Lipids may influence cellular penetrance by pathogens and the immune response that they evoke. Here we find a broad based lipidomic storm driven predominantly by secretory (s) phospholipase A2 (sPLA2) dependent eicosanoid production occurs in patients with sepsis of viral and bacterial origin and relates to disease severity in COVID-19. Elevations in the cyclooxygenase (COX) products of arachidonic acid (AA), PGD2 and PGI2, and the AA lipoxygenase (LOX) product, 12-HETE, and a reduction in 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, correlate with the inflammatory response and link to disease severity. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflect disease severity in COVID-19. AA and LA metabolites and LPC-O-16:0 linked variably to the immune response. These studies yield prognostic biomarkers and therapeutic targets for patients with sepsis, including COVID-19. An interactive purpose built interactive network analysis tool was developed, allowing the community to interrogate connections across these multiomic data and generate novel hypotheses.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 02, 2023.
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Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis
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 B. Meyer, Garret A. FitzGerald
bioRxiv 2023.06.02.543298; doi: https://doi.org/10.1101/2023.06.02.543298
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Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis
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 B. Meyer, Garret A. FitzGerald
bioRxiv 2023.06.02.543298; doi: https://doi.org/10.1101/2023.06.02.543298

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