Omega 3 Fatty Acids and COVID-19: A Comprehensive Review

Abstract

The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to "cytokine storm". This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.

Keywords: COVID-19; Docosahexaenoic acid; Eicosapentaenoic acid; Omega-3 fatty acids; SARS-CoV-2.

Figure 1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein binds with host cell angiotensin converting enzyme 2 (ACE-2) receptor. Subsequently, the virus enters the host cell either through membrane fusion or endocytosis and releases its positive sense ribonucleic acid (RNA) in the host cell cytoplasm via uncoating. The host ribosomes translate viral polymerase protein from positive sense RNA. The viral polymerase replicates negative sense RNA from the positive sense RNA. The viral polymerase then utilizes negative sense genome to produce more positive sense RNA (genomic replication) and mRNAs for nucleocapsid (N), spike (S), membrane (M), envelope (E) (subgenomic transcription). After the translation of viral structural proteins, S, E, and M proteins are processed in Endoplasmic Reticulum-Golgi (ERG) intermediate compartment. Nucleocapsids are assembled in the cytoplasm and then bud into the lumen of the ERG intermediate compartment. Finally, the mature virus inside the Golgi vesicle is released from the infected cell through exocytosis. A mature virus is capable of infecting the lung, endothelium, intestine, heart, testis, kidney through ACE-2 receptors.

Figure 2. How omega-3 fatty acids impact the cellular immune response.

Nuclear factor kappa B (NF-κB) is a pro-inflammatory cytokine triggering an inflammatory response via activation of transcription of genes for further pro-inflammatory proteins. Omega-3 fatty acids potentially exert their anti-inflammatory effect via toll-like receptor 4 (TLR4) pathway and G-protein coupled receptor 120 (GPR120) pathway to inhibit the NF-κB and consequently the inflammatory cascade. TAB, TGF-beta activated kinase; TAK, tat-associated kinase; IRAK, interleukin 1 receptor-associated kinase; TRAF6, tumor necrosis factor receptor associated factor 6; TRIAP, TP53 regulated inhibitor of apoptosis; MD2, myeloid differentiation factor 2.

Figure 3. Omega-3 fatty acid acting on different elements of the immune response.

Omega-3 fatty acids, through their anti-inflammatory mechanism, inhibit the production of pro-inflammatory mediators like interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and prevent cytokine storm. Some studies also suggest that they dampen the inflammatory response through regulatory T cells (Treg) differentiation. They also exert an anti-viral effect by enhancing the phagocytic activity of cells of the innate immune system- Neutrophils and Macrophages.

Figure 4. The global view of omega-3 index levels is shown in this figure.

The omega-3 index risk zones are as follows: ● High Risk ≤ 4%. ● Intermediate risk = 4 - 8%. ● Low risk > 8%.