Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection

Abstract

Obesity is a major independent risk factor for increased morbidity and mortality upon infection with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which is responsible for the current coronavirus disease pandemic (COVID-19). Therefore, there is a critical need to identify underlying metabolic factors associated with obesity that could be contributing toward increased susceptibility to SARS-CoV-2 in this vulnerable population. Here, we focus on the critical role of potent endogenous lipid metabolites known as specialized pro-resolving mediators (SPMs) that are synthesized from polyunsaturated fatty acids. SPMs are generated during the transition of inflammation to resolution and have a vital role in directing damaged tissues to homeostasis; furthermore, SPMs display anti-viral activity in the context of influenza infection without being immunosuppressive. We cover evidence from rodent and human studies to show that obesity, and its co-morbidities, induce a signature of SPM deficiency across immunometabolic tissues. We further discuss how the effects of obesity upon SARS-CoV-2 infection are likely exacerbated with environmental exposures that promote chronic pulmonary inflammation and augment SPM deficits. Finally, we highlight potential approaches to overcome the loss of SPMs using dietary and pharmacological interventions. Collectively, this mini-review underscores the need for mechanistic studies on how SPM deficiencies driven by obesity and environmental exposures may exacerbate the response to SARS-CoV-2.

Dietary Fish, Fish Nutrients, and Immune Function: A Review

“…Studies in mice models of acute infection have found that a high dietary intake of ω3-PUFAs significantly reduces IFN-gamma secretion ( 16 ). In fact, it has been hypothesized that some of the increased susceptibility of individuals with obesity to adverse outcomes after SARS-CoV-2 infection may be a consequence of their relative deficiency of SPMs derived from ω3-PUFAs ( 17 ). Furthermore, a recent proof-of-concept randomized trial in 100 patients with symptomatic COVID disease evaluated the effect of supplementation with icosapent ethyl, a highly purified preparation of EPA, on inflammation and symptomatology over 14 days.…”

Role of specialized pro-resolving lipid mediators and their receptors in virus infection: a promising therapeutic strategy for SARS-CoV-2 cytokine storm

“…Obesity is a risk factor for SARS-CoV-2 infection, and a BMI of 30 kg/m 2 increases the risk of infection by 61% (Bello-Chavolla et al 2020 ). This is likely due to a deficiency of SPMs in obese patients, and this deficiency promotes adverse reactions during SARS-CoV-2 infection (Pal et al 2020 ). LXA4, Elovanoid-N32 or RvD6 isomers reduced expression of angiotensin-converting enzyme 2 (ACE2), but NDP1 did not reduce it.…”

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

“…coli as well as regulate leukocyte transcripts of interest in infections. Hence, the nutritional availability of dietary n-3 PUFA and marine oils enriched with the SPM intermediate precursors (e.g., 17-HDHA, 18HEPE), along with increasing local biosynthesis of SPMs [ 26 ] to functional concentrations maybe an approach of value during Covid-19 as well as in prevention and shortening their recovery phase from infections.…”

“…In today’s diet 72% of calories come from foods that were not present during evolution [ 8 ]. In the meantime, physicians should consider measuring PUFAs and their potent cellular effectors both the eicosanoids and SPMs, in patients with Covid-19 and in patients with chronic diseases as in refs [ 24 , 25 , 26 , 28 ], specifically obesity, type 2 diabetes, hypertension and CHD by measuring LA, ALA, and the LA/ALA ratio, ARA+EPA+DHA and ARA/EPA+DHA ratio in red blood cell membrane phospholipids (RBC’s) and aim for balance in the dietary intake of n-6 and n-3 PUFA. FDA should not continue to list PUFA on the food label and should replace the term “PUFA” with actual amounts of the individual molecules namely LA, ALA, ARA, EPA and DHA, and eventually industry should adopt an n-6/n-3 “ratio” per serving in all processed foods [ 34 ].…”