High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients

FASEB J. 2021 Jun;35(6):e21666. doi: 10.1096/fj.202100540R.


Severe acute respiratory syndrome coronavirus 2 is responsible for coronavirus disease 2019 (COVID-19). While COVID-19 is often benign, a subset of patients develops severe multilobar pneumonia that can progress to an acute respiratory distress syndrome. There is no cure for severe COVID-19 and few treatments significantly improved clinical outcome. Dexamethasone and possibly aspirin, which directly/indirectly target the biosynthesis/effects of numerous lipid mediators are among those options. Our objective was to define if severe COVID-19 patients were characterized by increased bioactive lipids modulating lung inflammation. A targeted lipidomic analysis of bronchoalveolar lavages (BALs) by tandem mass spectrometry was done on 25 healthy controls and 33 COVID-19 patients requiring mechanical ventilation. BALs from severe COVID-19 patients were characterized by increased fatty acids and inflammatory lipid mediators. There was a predominance of thromboxane and prostaglandins. Leukotrienes were also increased, notably LTB4 , LTE4 , and eoxin E4 . Monohydroxylated 15-lipoxygenase metabolites derived from linoleate, arachidonate, eicosapentaenoate, and docosahexaenoate were also increased. Finally yet importantly, specialized pro-resolving mediators, notably lipoxin A4 and the D-series resolvins, were also increased, underscoring that the lipid mediator storm occurring in severe COVID-19 involves pro- and anti-inflammatory lipids. Our data unmask the lipid mediator storm occurring in the lungs of patients afflicted with severe COVID-19. We discuss which clinically available drugs could be helpful at modulating the lipidome we observed in the hope of minimizing the deleterious effects of pro-inflammatory lipids and enhancing the effects of anti-inflammatory and/or pro-resolving lipid mediators.

Keywords: COVID-19; docosanoids; eicosanoids; eoxins; specialized pro-resolving mediators; thromboxane.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • COVID-19* / metabolism
  • COVID-19* / pathology
  • COVID-19* / therapy
  • Female
  • Humans
  • Leukotriene B4 / metabolism*
  • Leukotriene E4 / analogs & derivatives*
  • Leukotriene E4 / metabolism*
  • Lipoxins / metabolism*
  • Lung* / metabolism
  • Lung* / pathology
  • Lung* / virology
  • Male
  • Middle Aged
  • SARS-CoV-2 / metabolism*


  • 14-cysteinyl-15-hydroxy-5,8,10,12-eicosatetraenoic acid
  • Lipoxins
  • lipoxin A4
  • Leukotriene B4
  • Leukotriene E4