Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Daniel P. Pike, Reagan M. McGuffee, Elizabeth Geerling, Carolyn J. Albert, Daniel F. Hoft, Michael G.S. Shashaty, Nuala J. Meyer, Amelia K. Pinto, David A. Ford

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Plasmalogens are plasma-borne antioxidant phospholipid species that provide protection as cellular lipid components during cellular oxidative stress. In this study we investigated plasma plasmalogen levels in human sepsis as well as in rodent models of infection. In humans, levels of multiple plasmenylethanolamine molecular species were decreased in septic patient plasma compared to control subject plasma as well as an age-aligned control subject cohort. Additionally, lysoplasmenylcholine levels were significantly decreased in septic patients compared to the control cohorts. In contrast, plasma diacyl phosphatidylethanolamine and phosphatidylcholine levels were elevated in septic patients. Lipid changes were also determined in rats subjected to cecal slurry sepsis. Plasma plasmenylcholine, plasmenylethanolamine, and lysoplasmenylcholine levels were decreased while diacyl phosphatidylethanolamine levels were increased in septic rats compared to control treated rats. Kidney levels of lysoplasmenylcholine as well as plasmenylethanolamine molecular species were decreased in septic rats. Interestingly, liver plasmenylcholine and plasmenylethanolamine levels were increased in septic rats. Since COVID-19 is associated with sepsis-like acute respiratory distress syndrome and oxidative stress, plasmalogen levels were also determined in a mouse model of COVID-19 (intranasal inoculation of K18 mice with SARS-CoV-2). 3 days following infection, lung infection was confirmed as well as cytokine expression in the lung. Multiple molecular species of lung plasmenylcholine and plasmenylethanolamine were decreased in infected mice. In contrast, the predominant lung phospholipid, dipalmitoyl phosphatidylcholine, was not decreased following SARS-CoV-2 infection. Additionally total plasmenylcholine levels were decreased in the plasma of SARS-CoV-2 infected mice. Collectively, these data demonstrate the loss of plasmalogens during both sepsis and SARS-CoV-2 infection. This study also indicates plasma plasmalogens should be considered in future studies as biomarkers of infection and as prognostic indicators for sepsis and COVID-19 outcomes.

Original languageEnglish
Article number912880
JournalFrontiers in Cell and Developmental Biology
StatePublished - Jun 6 2022

Bibliographical note

Funding Information:
This study was supported (in part) by research funding from the National Institutes of Health R01 GM-115553 and S10OD025246 to DF. Clinical samples and patient phenotyping were funded by NIH HL137006 and HL137915 to NM.

Publisher Copyright:
Copyright © 2022 Pike, McGuffee, Geerling, Albert, Hoft, Shashaty, Meyer, Pinto and Ford.


  • infection
  • inflammation
  • lipidomics
  • plasmalogen
  • SARS-CoV-2
  • sepsis

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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