Polyunsaturated Fatty Acids Reduce Risk Of Severity – Hospitalizations And Mortality In COVID-19

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A new study by researchers from Shiraz University of Medical Sciences-Iran And Birjand University of Medical Science-Iran has found that polyunsaturated fatty acids (PUFAs) reduce risk of severity, hospitalizations and mortality in COVID-19.

The study findings were published in the peer reviewed journal: Life Scienceshttps://www.sciencedirect.com/science/article/pii/S0024320522001898

Covid-19 is an acute respiratory syndrome disease caused by SARS-COV-2, which was introduced as a pandemic in early 2020 and has been diagnosed in more than 230 million people worldwide by September 2021 [1], [2]. The disease worsens with age (especially over 60 years), male sex, and underlying diseases and its mortality is largely associated with rapidly increasing inflammatory cytokines, including interleukin-6 (IL-6) [3].

In SARS-CoV-2 infection, excessive and uncontrolled production of pro-inflammatory cytokines by innate immune cells, intensify secretion of other pro-inflammatory chemical agents such as vascular endothelial growth factor (VEGF), MCP-1, interleukin-8 (IL-8) while reduce the expression of E-cadherin in endothelial cells [4].

VEGF and decreased E-cadherin expression contribute to permeability and vascular leakage, leading to pulmonary dysfunction (ALI), acute respiratory syndrome (ARDS) and ultimately systemic inflammation and multiple organ failure in individuals infected with covid-19 [4], [5], [6].

Thus, cytokine storms are considered as a key factor in disease control, which can exacerbate COVID-19 and even cause mortality. Accordingly, a prophylactic approach to prevent the covid-19 infection is to minimize the release of inflammatory cytokines [3]. Poly unsaturated fatty acids (PUFAs) are an integral component of cell membrane and play an important role in the structural integrity and fluidity of membrane phospholipids.

In addition to PUFAs antioxidant function, they play an important role in modulating immune pathways and inflammatory responses which can be helpful in the treatment of viral diseases with a tendency to increase inflammatory cytokines [7], [8], [9].

PUFAs include omega-3 PUFA and omega-6 PUFA which the former acids originate from natural sources and include alpha linoleic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [2], [3] and the latter one, mainly contain linoleic acid (LA) and arachidonic acid (AA) [10].

Up to 25% of the fatty acids in the phospholipids of skeletal muscles, brain, liver, platelets, and immune cells can be attributed to AA [11]. The interaction of AA with molecular oxygen produces mediators known as eicosanoids, which include prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs) [12], [13].

In the presence of certain stimuli such as inflammatory stimuli, enough AA is released to cause significant increases in eicosanoid production. In this situation eicosanoids such as PGD2 and E2, as well as 4-series LTs, are produced in greater quantities and serve as mediators and regulators of the inflammatory response [12].

Recent studies has revealed that omega-3 PUFAs are significant mediators of inflammation that can amplify anti-inflammatory responses, block hyper inflammatory reactions, reduce the incidence of systemic inflammatory response syndrome (SIRS), and complications of infection [14], [15]. One of the anti-inflammatory effects of EPA and DHA is reduced activation of the NF-κB pro-inflammatory transcription factor in response to inflammatory stimuli. This effect has been linked to EPA and DHA’s membrane-mediated actions, which block the early phases of inflammatory signaling [16], [17].

However, it appears that EPA and DHA can reduce inflammatory responses by acting directly on inflammatory cells via membrane receptors. For instance binding long-chain fatty acids, especially DHA to GPR120 receptor in macrophages reduce NF_κB activation and decrease the production of inflammatory cytokines.

This mechanism of action suggests that EPA and DHA can have anti-inflammatory effects without having to be incorporated into cell membranes or affecting lipid mediator production [18]. Also, Omega-3 fatty acids are thought to give rise to mediators referred to as specialized pro-resolving mediators (SPMs).

SPMs including resolvins, protectins and maresins activate the resolution of inflammation in various diseases [9], [19], [20], [21], [22]. In addition, omga-3 fatty acids are involved in regulating the activation of immune cells, including macrophages, neutrophils, basophils, eosinophils, T and B cells.

Studies have shown that omega-3 fatty acids are present in neutrophil cell membrane phospholipids, and by secreting cytokines and chemokines improve macrophage function and increase phagocytic ability, thereby enhancing immune function [23]. These findings show that omega-3 fatty acids might be effective as a pharmaconutrient in lowering the impact of inflammation produced by COVID-19 [24].

Given the public health concerns the current covid-19 epidemic and its mortality, it is necessary to investigate modifiable risk factors for severe complications of inflammatory storm. One of the possible preventives and relatively cost-effective methods for high-risk patients can be the use of diets and supplements rich in unsaturated fatty acids, especially omega-3 PUFA. According to the contradictory results obtained from various studies, the present study has been reviewed the studies to find out the possible role of polyunsaturated fatty acids in the severity of Covid-19 disease.

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