Possibility of averting cytokine storm in SARS-COV 2 patients using specialized pro-resolving lipid mediators.

Fatal "cytokine storms (CS)" observed in critically ill COVID-19 patients are consequences of dysregulated host immune system and over-exuberant inflammatory response. Acute respiratory distress syndrome (ARDS), multi-system organ failure, and eventual death are distinctive symptoms, attributed to higher morbidity and mortality rates among these patients. Consequent efforts to save critical COVID-19 patients via the usage of several novel therapeutic options are put in force. Strategically, drugs being used in such patients are dexamethasone, remdesivir, hydroxychloroquine, etc. along with the approved vaccines. Moreover, it is certain that activation of the resolution process is important for the prevention of chronic diseases. Until recently Inflammation resolution was considered a passive process, rather it's an active biochemical process that can be achieved by the use of specialized pro-resolving mediators (SPMs). These endogenous mediators are an array of atypical lipid metabolites that include Resolvins, lipoxins, maresins, protectins, considered as immunoresolvents, but their role in COVID-19 is ambiguous. Recent evidence from studies such as the randomized clinical trial, in which omega 3 fatty acid was used as supplement to resolve inflammation in COVID-19, suggests that direct supplementation of SPMs or the use of synthetic SPM mimetics (which are still being explored) could enhance the process of resolution by regulating the aberrant inflammatory process and can be useful in pain relief and tissue remodeling. Here we discussed the biosynthesis of SPMs, & their mechanistic pathways contributing to inflammation resolution along with sequence of events leading to CS in COVID-19, with a focus on therapeutic potential of SPMs.

Clostridium butyricum-induced ω-3 fatty acid 18-HEPE elicits anti-influenza virus pneumonia effects through interferon-λ upregulation.

The precise mechanism by which butyrate-producing bacteria in the gut contribute to resistance to respiratory viral infections remains to be elucidated. Here, we describe a gut-lung axis mechanism and report that orally administered Clostridium butyricum (CB) enhances influenza virus infection resistance through upregulation of interferon (IFN)-λ in lung epithelial cells. Gut microbiome-induced ω-3 fatty acid 18-hydroxy eicosapentaenoic acid (18-HEPE) promotes IFN-λ production through the G protein-coupled receptor (GPR)120 and IFN regulatory factor (IRF)-1/-7 activations. CB promotes 18-HEPE production in the gut and enhances ω-3 fatty acid sensitivity in the lungs by promoting GPR120 expression. This study finds a gut-lung axis mechanism and provides insights into the treatments and prophylaxis for viral respiratory infections.

Omega-3 Polyunsaturated Fatty Acids Protect against High-Fat Diet-Induced Morphological and Functional Impairments of Brown Fat in Transgenic Fat-1 Mice.

The role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the regulation of energy homeostasis remains poorly understood. In this study, we used a transgenic fat-1 mouse model, which can produce n-3 PUFAs endogenously, to investigate how n-3 PUFAs regulate the morphology and function of brown adipose tissue (BAT). We found that high-fat diet (HFD) induced a remarkable morphological change in BAT, characterized by "whitening" due to large lipid droplet accumulation within BAT cells, associated with obesity in wild-type (WT) mice, whereas the changes in body fat mass and BAT morphology were significantly alleviated in fat-1 mice. The expression of thermogenic markers and lypolytic enzymes was significantly higher in fat-1 mice than that in WT mice fed with HFD. In addition, fat-1 mice had significantly lower levels of inflammatory markers in BAT and lipopolysaccharide (LPS) in plasma compared with WT mice. Furthermore, fat-1 mice were resistant to LPS-induced suppression of UCP1 and PGC-1 expression and lipid deposits in BAT. Our data has demonstrated that high-fat diet-induced obesity is associated with impairments of BAT morphology (whitening) and function, which can be ameliorated by elevated tissue status of n-3 PUFAs, possibly through suppressing the effects of LPS on inflammation and thermogenesis.

Advances in muscle health and nutrition: A toolkit for healthcare professionals.

Low muscle mass and malnutrition are prevalent conditions among adults of all ages, with any body weight or body mass index, and with acute or chronic conditions, including COVID-19. This article synthesizes the latest research advancements in muscle health and malnutrition, and their impact on immune function, and clinical outcomes. We provide a toolkit of illustrations and scientific information that healthcare professionals can use for knowledge translation, educating patients about the importance of identifying and treating low muscle mass and malnutrition. We focus on the emerging evidence of mitochondrial dysfunction in the context of aging and disease, as well as the cross-talk between skeletal muscle and the immune system. We address the importance of myosteatosis as a component of muscle composition, and discuss direct, indirect and surrogate assessments of muscle mass including ultrasound, computerized tomography, deuterated creatine dilution, and calf circumference. Assessments of muscle function are also included (handgrip strength, and physical performance tests). Finally, we address nutrition interventions to support anabolism, reduce catabolism, and improve patient outcomes. These include protein and amino acids, branched-chain amino acids, with a focus on leucine; ß-hydroxy-ß-methylbutyrate (HMB), vitamin D; n-3 polyunsaturated fatty acids (n-3 PUFA), polyphenols, and oral nutritional supplements. We concluded with recommendations for clinical practice and a call for action on research focusing on evaluating the impact of body composition assessments on targeted nutrition interventions, and consequently their ability to improve patient outcomes.

Four-week omega-3 polyunsaturated fatty acids supplementation for liver left lateral section volume reduction in individuals with morbid obesity undergoing bariatric surgery: A double blind, multicenter, randomized placebo-controlled trial.

BACKGROUND: Liver steatosis in morbidly obese individuals undergoing bariatric surgery increases liver volume and may complicate the surgical procedure. This study aimed to assess whether a 4-week supplementation with omega-3 polyunsaturated fatty acids (PUFA) is effective in reducing liver left lateral section (LLLS) volume. PATIENTS AND METHODS: This randomized controlled trial included morbidly obese individuals with metabolic syndrome undergoing bariatric surgery at 3 French bariatric centers between 2017 and 2020. The experimental group had a 4-week preoperative supplementation with omega-3 PUFA, whereas the control group had only placebo. The primary outcome was the reduction of the LLLS volume measured with Magnetic Resonance Imaging (MRI). RESULTS: 42 patients were randomized and 37 completed the study (19 in the experimental group and 18 in the placebo group). The mean LLLS volume decreased of 3.3% (±9.6) in the experimental group vs 1.0% (±18.3) in the placebo group, indicating that omega-3 PUFA were not effective in reducing the LLLS volume compared to the placebo (p = 0.3741). Omega-3 PUFA supplementation was not effective in reducing total liver volume, liver steatosis, rate of liver injuries during surgery and operative time. CONCLUSION: A 4-week preoperative supplementation with omega-3 PUFA was not effective in reducing LLLS volume in morbidly obese individuals undergoing bariatric surgery.

Effects of Omega-3 Polyunsaturated Fatty Acids and Their Metabolites on Haemostasis-Current Perspectives in Cardiovascular Disease.

The beneficial effects of long-chain polyunsaturated omega-3 fatty acids (omega-3 PUFAs) in cardioprotection are widely known and generally accepted. In this literature review, we have focused on the known and postulated mechanisms of action of omega-3 PUFAs and their metabolites on various components of the haemostatic system, in particular on blood platelets and endothelium. We have also made an attempt to provide a comprehensive review of epidemiological studies with particular regard to clinical trials. Notably, the results of these studies are contradictory, and some of them failed to report the beneficial effects of taking or supplementing omega-3 PUFAs in the diet. A potential explanation, in our opinion, could be the need to use higher doses of omega-3 PUFAs and a proper ratio of omega-3 and omega-6 PUFAs. An additional problem which is difficult to solve is the use of a proper neutral placebo for interventional studies. Despite some controversies regarding the beneficial effects of supplementation of omega-3 PUFAs in cardiovascular disease, our review suggests that a promising aspect of future studies and applications is to focus on the anti-thrombotic properties of these compounds. An argument supporting this assumption is the recent use of omega-3 PUFAs as a supporting tool for the treatment of COVID-19 complications.

The need for precision nutrition, genetic variation and resolution in Covid-19 patients.

The health of the individual and the population in general is the result of interaction between genetics and various environmental factors, of which diet/nutrition is the most important. The focus of this paper is on the association of high n-6 PUFA or low n-3 PUFA due to genetic variation and/or dietary intake, with changes in specialized pro-resolving mediators (SPMs), cytokine storm, inflammation-resolution and Covid-19. Human beings evolved on a diet that was balanced in the n-6 and n-3 essential fatty acids with a ratio of n-6/n-3 of 1-2/1 whereas today this ratio is 16/1. Such a high ratio due to high amounts of n-6 fatty acids leads to a prothrombotic and proinflammatory state and is associated with obesity, diabetes, cardiovascular disease, and some forms of cancer. In addition to the high intake of n-6 fatty acids that increases inflammation there is genetic variation in the biosynthesis of n-6 linoleic acid (LA) to arachidonic acid (ARA) and of linolenic (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Present day humans have two common FADS haplotypes that differ dramatically in their ability to generate long-chain fatty acids. The more efficient, evolutionary derived haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and could have provided an advantage in environments with limited access to dietary long-chain fatty acids ARA, EPA and DHA. In the modern world this haplotype has been associated with lifestyle-related diseases, such as cardiovascular disease, obesity, diabetes, all of which are characterized by increased levels of inflammation. African Americans and Latino populations have increased susceptibility and higher death rates from SARS-CoV-2 than whites. These populations are characterized by increased numbers of persons (about 80%) that are fast metabolizers, leading to increased production of ARA, as well as poor intake of fruits and vegetables. The combinations of fast metabolism and high n-6 intake increases their inflammatory status and possibly susceptibility of SARS-CoV-2. In vitro and human studies indicate that the specialized pro-resolving mediators (SPM) produced from the n-3, EPA and DHA influence the resolution of inflammation, allowing the tissues to return to function and homeostasis. The SPMs each counter-regulate cytokine storms, as well as proinflammatory lipid mediators via NFκB and inflammasome down regulation and reduce the proinflammatory eicosanoids produced from ARA. The nutritional availability of dietary n-3 fatty acids from marine oils enriched with SPM intermediate precursors, along with increasing local biosynthesis of SPMs to functional concentrations may be an approach of value during SARS-CoV2 infections, as well as in prevention, and shortening their recovery from infections. It is evident that populations differ in their genetic variants and their frequencies and their interactions with the food they eat. Gene-nutrient interactions is a very important area of study that provides specific dietary advice for individuals and subgroups within a population in the form of Precision Nutrition. Nutritional science needs to focus on Precision Nutrition, genetic variants in the population and a food supply composed of Nutrients that have been part of our diet throughout evolution, which is the diet that our genes are programmed to respond.

Omega-3 fatty acids in the psychological and physiological resilience against COVID-19.

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.

Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work.

BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.