8.5  N-3 PUFAs possess anti-oxidant properties
The pneumonia-induced hypoxemia caused by RNA virus infections reduces the energy production from cell metabolism, increases the anaerobic fermentation, intracellular acidosis and the generation of ROS (Li et al., 2020). The subsequent increased ROS production causes damage to different cellular components including the DNA, lipids and proteins. The increased ROS levels will deplete the antioxidant defense system resulting in severe oxidative stress and chronic activation of immune responses, aggravating tissue injury and damage (Khomich, Kochetkov, Bartosch, & Ivanov, 2018; Reshi, Su, & Hong, 2014).
Several studies reveal n-3 PUFAs possess anti-oxidant properties attributable to their ability to up-regulate anti-oxidant enzymes (e.g. superoxide dismutase), down-regulate pro-oxidant enzymes (e.g. nitric oxide synthase) and potential to interact directly with free radicals. Antioxidant effects of n-3 PUFAs have been demonstrated in different organs including lungs, kidneys and the cardiovascular system (Darwesh et al., 2020; Darwesh, Jamieson, et al., 2019; Darwesh, Keshavarz-Bahaghighat, et al., 2019; De Caterina, 2011; Mozaffarian & Wu, 2011). Anderson et al. reported patients were administered a moderately high dose of n-3 PUFAs (3.4 g/day EPA and DHA ethyl-esters) for a period of 2–3 weeks before having elective cardiac surgery and then myocardial tissue was dissected from the right atrium during surgery. Intriguingly, myocardial tissues obtained from patients displayed improved antioxidant capacity attributed to increased expression and activity of key antioxidants such as glutathione peroxidase-1, glutathione peroxidase-4, NADPH-quinone oxido-reductase-1, thioredoxin reductase-2 and total glutathione compared to the control patients. Moreover, the mitochondrial outer membrane-bound enzyme monoamine oxidase, a substantial generator of ROS, was also determined to have significantly lower activity in myocardial tissue obtained from n-3 PUFA-treated patients (Anderson et al., 2014). Interestingly, isolated mouse hearts perfused with DHA derived epoxylipids had improved postischemic recovery which correlated with better activities of the antioxidants thioredoxin-1 and thioredoxin-2 (Darwesh, Jamieson, et al., 2019). Importantly, with COVID-19, especially in advanced stages and in ICU, severe inflammation, hypoxemia and mechanical ventilation with high oxygen concentrations will inevitably increase ROS generation locally and systemically notably within the lungs and the heart. Thus, it can be hypothesized that increased n-3 PUFAs and their corresponding metabolites would provide beneficial control of exaggerated inflammation and ROS production.