The cytokine storm present in COVID-19 in obese patients (and normal-weight patients) develops acute respiratory distress syndrome (ARDS). This syndrome is characterized by a severe hypoxic respiratory failure due to an exacerbated inflammatory reaction and can lead to multi-organ dysfunction. Indeed, this is the battle we fight every day in the hospitals. Unfortunately, up to date, there are no effective pharmacotherapies to diminish the disease progress of ARDS, leading to prolonged intrahospital stay and invasive mechanical ventilation. However, preventive and counteracting strategies can apply to the ARDS care setting. The immunomodulatory effects of omega-3 fatty acids can substantially reduce mortality and improve oxygenation by suppressing the synthesis of pro-inflammatory eicosanoids. Once again, preventive use of immunonutrition reduces the detrimental effects of COVID-19 in obese patients.

ARDS:

The presence of ARDS affects the lung epithelial and endothelial function leading to alveolar-capillary permeability and pulmonary edema. A lot of things have changed since the first clinical description of ARDS in 1967. Nowadays, the “Berlin Definition” set by an expert consensus created this criterion:

1. Onset within seven days of a known clinical insult.
2. Bilateral opacities on chest imaging.
3. PaO₂/FiO₂ ratio is less than 300 mmHg.
4. Hypoxaemia is not fully explained by cardiac failure or fluid overload.

Immunonutrition: Omega-3 fatty acids.

In a disease context, our body produces an excess of reactive oxygen species. If we add to this equation the pro-inflammatory cytokines synthesized by the excessive fat content, we create a pro-oxidant and pro-inflammatory environment. Consequently, the pharmaconutrients used by immunonutrition act to counteract this environment by promoting anti-inflammatory and anti-oxidant reactions. Indeed, Omega-3 fatty acids can enable both of these protective effects.

As a preventive measure, the intake of omega-3 fatty acids by its primary dietary source, fish, can promote an anti-inflammatory milieu by promoting the synthesis of resolvins and protectins. Resolvins, protectins, and maresins are known as specialized pro-resolvins mediators. Current research shows that these molecules, combined with other immune mediators, improve the cytokine storm associated with ARDS.

Resolvins, Inflammatory Response, Immune cells, and Mobility:

An acute inflammatory response is crucial for initial protection against pathogens and injury. As a member of first responders to a provocative call, neutrophils can phagocytize microbes and eliminate cellular debris. However, this reaction can potentially damage cellular tissue exacerbating the inflammatory response and creating low-grade inflammation. This reaction happens when neutrophils (polymorphonuclear leukocytes PMNs) congregate in tissues and release antimicrobial factors due to frustrated phagocytosis or cell death. Consequently, this “unnecessary roughness” leads to tissue damage. Therefore, the resolution of the first acute inflammatory response is essential to prevent chronic diseases.

A healthy nutritional status associates with a self-limited acute inflammatory response that will resolve on its own. Furthermore, this resolution depends on lipoxins that serve as “stop” signals for the inflammatory response.

To link it all together, resolvins, protectins, and maresins can reduce osteoarthritic pain, particularly At-TvD1. Therefore, the supplementation of omega-3 fatty acids and the dietary intake of fish coincide with elevated levels of SPMs in plasma. In turn, increased levels of resolvins have a tight association with lower levels of RA- associated pain and inflammatory markers. Also, this coincides with an increase in mobility by lowering baseline pain and reduced the risk of infection.

The use of omega-3 fatty acids in immunonutrition has direct causation with reduced intrahospital stay and a lower risk of infections. However, in the context of two global epidemics with interacting complications founded on low-grade inflammation, what can immunonutrition do to help? The main related protective effect of immunonutrition and omega-3 fatty acids is their ability to increase protectin levels. In turn, this production of protectins creates an overlap of benefits by reducing pain and improving mobility, which translates to more muscle and less fatty tissue. Also, this improvement in mobility reflects in less intrahospital stay, lower risk of infection, fewer costs, and less adipose-associated inflammation. Bottom line: eat your fish, take your omega-3, and exercise! – Ana Paola Rodríguez Arciniega, MS

References:

Dushianthan, Ahilanandan et al. “Immunonutrition for acute respiratory distress syndrome (ARDS) in adults.” The Cochrane database of systematic reviews vol. 1,1 CD012041. 24 Jan. 2019, doi:10.1002/14651858.CD012041.pub2

Di Renzo, Laura et al. “COVID-19: Is there a role for immunonutrition in obese patient?.” Journal of translational medicine vol. 18,1 415. 7 Nov. 2020, doi:10.1186/s12967-020-02594-4

Serhan, C. N., & Levy, B. D. (2018). Resolvins in inflammation: the emergence of the pro-resolving superfamily of mediators. The Journal of clinical investigation, 128(7), 2657–2669. doi.org/10.1172/JCI97943

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