May omega-3 fatty acid dietary supplementation help reduce severe complications in Covid-19 patients?

Abstract

In around 10% of SARS-CoV-2 infected patients, coronavirus disease-2019 (Covid-19) symptoms are complicated with a severe lung damage called Acute Respiratory Distress Syndrome (ARDS), which is often lethal. ARDS is mainly associated with an uncontrolled overproduction of immune cells and cytokines, called "cytokine storm syndrome"; it appears 7-15 days following the onset of symptoms, leading to systemic inflammation and multiple organ failure. Because they are well-known metabolic precursors of specialized pro-resolving lipid mediators (SPMs), omega-3 long-chain polyunsaturated fatty acids (omega-3 LC-PUFAs) could help improve the resolution of the inflammatory balance, limiting therefore the level and duration of the critical inflammatory period. Omega-3 LC-PUFAs may also interact at different stages of the viral infection, notably on the virus entry and replication. In the absence of demonstrated treatment and while waiting for vaccine possibility, the use of omega-3 LC-PUFAs deserve therefore to be considered, based on previous clinical studies suggesting that omega-3 supplementation could improve clinical outcomes of critically ill patients at the acute phase of ARDS. In this context, it is crucial to remind that the omega-3 PUFA dietary intake levels in Western countries remains largely below the current recommendations, considering both the omega-3 precursor α-linolenic acid (ALA) and long chain derivatives such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). An optimized omega-3 PUFAs status could be helpful to prevent infectious diseases, including Covid-19.

Keywords: Docosopentaenoic acid; Eicosapentaenoic acid; Immunity; Lipid; Virus; α-linolenic acid.

Fig. 1

– Expected mechanisms of the anti-inflammatory effect of omega-3 long chain polyunsaturated fatty acids (omega-3 LC-PUFAs) and cytokine storm prevention during the Coronavirus disease-2019. General population has deficiency in Omega-3 LC-PUFAs that increases proportion of arachidonic acid (ARA) from Omega-6 PUFA family in phospholipid membranes of the cells. ARA is liberated from its sn-2 position by the phospholipase A2 (PLA2) and become a substrate for cyclooxygenase enzymes (COX1 and COX2). Prostaglandins E2 (PGE2) is synthesized from ARA and is pro-inflammatory by activating NF-κB and lead to systemic chronic low-grade inflammation and a higher response to severe acute inflammation. A nutritional supplementation in omega-3 fatty acids may decrease or even remove the deficiency in population. This supplementation will increase eicosapentaenoic acid (EPA), omega-3 DPA and docosahexaenoic acid (DHA) proportion in phospholipid membranes of the cells. EPA, DPA and DHA are, like ARA, liberated by PLA2. It is a limiting step for the synthesis of lipid mediators from PUFAs. EPA is a substrate for COX enzymes and also lipoxygenases (LOX). PGE3 and E-series resolvins are produced from EPA and have anti-inflammatory properties. DHA is a substrate for LOX and produces D-series resolvins, protectins and maresins that have anti-inflammatory properties. These specialized pro-resolving mediators from EPA and DHA, in a case of acute inflammation by activation of NF-κB, will activate peroxisome proliferator-activated receptor (PPAR)-γ. PPAR-γ inhibits NF-κB. Consequently, the production of pro-inflammatory cytokines is reduced and may prevent cytokine storm.