Abstract
Polyunsaturated fatty acids are metabolized into regulatory lipids important for initiating inflammatory responses in the event of disease or injury and for signaling the resolution of inflammation and return to homeostasis. The epoxides of linoleic acid (leukotoxins) regulate skin barrier function, perivascular and alveolar permeability and have been associated with poor outcomes in burn patients and in sepsis. It was later reported that blocking metabolism of leukotoxins into the vicinal diols ameliorated the deleterious effects of leukotoxins, suggesting that the leukotoxin diols are contributing to the toxicity. During quantitative profiling of fatty acid chemical mediators (eicosanoids) in COVID-19 patients, we found increases in the regioisomeric leukotoxin diols in plasma samples of hospitalized patients suffering from severe pulmonary involvement. In rodents these leukotoxin diols cause dramatic vascular permeability and are associated with acute adult respiratory like symptoms. Thus, pathways involved in the biosynthesis and degradation of these regulatory lipids should be investigated in larger biomarker studies to determine their significance in COVID-19 disease. In addition, incorporating diols in plasma multi-omics of patients could illuminate the COVID-19 pathological signature along with other lipid mediators and blood chemistry.
Highlights
The pandemic coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initiates an aberrant immunological response resulting in a wide range of disease severities ranging from asymptomatic cases to severe cases with rapid progression to acute respiratory distress syndrome (ARDS) and death (Arentz et al, 2020; Du et al, 2020)
COVID-19 patients, they are lower than levels usually observed in non-COVID ARDS, suggesting additional factors lead to severe outcomes in some patients (Sinha et al, 2020)
One of the key pathways regulating the immune response to infections is the release of regulatory lipid mediators that have dual functions of driving inflammation [e.g., prostaglandins (PGE2)] or promoting resolution of inflammation and return to homeostasis [e.g., long chain epoxy fatty acids (EpFAs)] (Dennis and Norris, 2015; Hammock et al, 2020)
Summary
The pandemic coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initiates an aberrant immunological response resulting in a wide range of disease severities ranging from asymptomatic cases to severe cases with rapid progression to acute respiratory distress syndrome (ARDS) and death (Arentz et al, 2020; Du et al, 2020). Patients with severe COVID-19 show evidence of hyperinflammation with increased release of inflammatory cytokines (Pedersen and Ho, 2020). Recent reports demonstrate that, pro-inflammatory cytokine levels are elevated in severe. One of the key pathways regulating the immune response to infections is the release of regulatory lipid mediators that have dual functions of driving inflammation [e.g., prostaglandins (PGE2)] or promoting resolution of inflammation and return to homeostasis [e.g., long chain epoxy fatty acids (EpFAs)] (Dennis and Norris, 2015; Hammock et al, 2020). Recent data indicate a role of dysregulated lipid profiles in COVID19 and identified cytochrome P450 (CYP) metabolites of polyunsaturated fatty acids (PUFA) as potential biomarkers of disease severity (Hammock et al, 2020; Schwarz et al, 2020)
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