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. 2020 Sep;190(9):1782–1788. doi: 10.1016/j.ajpath.2020.06.010

Figure 1.

Figure 1

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to severe tissue damage, which releases cell debris. Both primary infection and the accumulation of cell debris initiate the endoplasmic reticulum (ER) stress response and up-regulate inflammatory enzymes, including microsomal prostaglandin E synthase-1 (mPGES-1) and prostaglandin-endoperoxide synthase 2 [cyclooxygenase 2 (COX-2)], which subsequently produce eicosanoids, including prostaglandins (PGs), leukotrienes (LTs), and thromboxanes (TXs). These proinflammatory lipid autacoids induce cytokine storms that mediate widespread inflammatory responses and organ damage in severe coronavirus disease 2019 (COVID-19) patients. By contrast, epoxyeicosatrienoic acids (EETs), which are stabilized by inhibition of their metabolizing enzyme, soluble epoxide hydrolase (sEH), are anti-inflammatory and proresolving mediators that promote the termination (resolution) of inflammation by suppressing the ER stress response, inflammatory enzyme induction, and proinflammatory cytokine production. EETs also shift arachidonic acid metabolism to favor the production of specialized proresolving mediators (SPMs), which initiate downstream anti-inflammatory and proresolving programs. EETs and sEH inhibitors may counterregulate the unabated systemic inflammatory response and organ failure associated with COVID-19 infection. DHET, dihydroxyeicosatrienoic acid; TNF-α, tumor necrosis factor-α.