scholarly journals Immunomodulation by intravenous omega-3 fatty acid treatment in older subjects hospitalized for COVID-19: a single-blind randomized controlled trial

Author(s):  
Hildur Arnardottir ◽  
Sven-Christian Pawelzik ◽  
Philip Sarajlic ◽  
Alessandro Quaranta ◽  
Johan Kolmert ◽  
...  

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) with respiratory distress and systemic hyperinflammation. The primary objective of this single-blind randomized controlled proof-of-concept clinical trial was to establish the effects of intravenous (i.v.) omega-3 (n-3) polyunsaturated fatty acid (PUFA) treatment compared to placebo on inflammatory markers in COVID-19, represented by leukocytes as well as inflammatory protein and lipid mediators. Here we also present an exploratory analysis of the mechanisms of action to elucidate the potential to resolve the COVID-19 hyperinflammation through interfering with lipid mediators. Inclusion criteria were COVID-19 diagnosis and clinical status requiring hospitalization. Randomization was 1:1 to a once daily i.v. infusion (2 mL/kg) of either n-3 PUFA emulsion containing 10g of fish oil per 100 mL or placebo (NaCl) for 5 days. Results from 22 older subjects (mean age 81±6.1 years) were analyzed. The neutrophil to lymphocyte ratio was significantly decreased after n-3 PUFA administration. Liquid chromatography–mass spectrometry (LC-MS/MS) -based lipid metabolite analysis established increased proresolving lipid mediator precursor levels and decreased formation of leukotoxin and isoleukotoxin diols by n-3 PUFA treatment. The mechanistic exploration revealed decreased immunothrombosis and preserved interferon-response. Finally, n-3 PUFA treatment may serve to limit cortisone-induced immunosuppression, including preserving leukocyte phagocytic capacity. In conclusion, i.v. n-3 PUFA administration was safe and feasible during hospitalization of multimorbid older subjects for COVID-19. The results identified n-3 PUFA treatment mediated lipid signature of increased proresolving precursor levels and decreased leukotoxin diols in parallel to beneficial immune responses. EudraCT: 2020-002293-28; clinicaltrials.gov: NCT04647604.

2020 ◽  
Vol 31 (2) ◽  
pp. 229
Author(s):  
ShirishK Kujur ◽  
Varsha Goswami ◽  
AnandM Nikunj ◽  
Gangesh Singh ◽  
Shweta Bandhe ◽  
...  

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Helena Fisk ◽  
Rob Ayres ◽  
Caroline Childs ◽  
Elizabeth Miles ◽  
Ondrej Kudak ◽  
...  

AbstractIntroduction:Obesity is an excess of adipose tissue (AT) and is linked with increased inflammation that enhances risk of type-2 diabetes and cardiovascular disease. The BIOCLAIMS study assessed the fatty acid (FA) and lipid mediator composition in normal weight and obese individuals, and their response to chronic omega-3 FA supplementation.Materials and methods:AT biopsies were collected pre- and post-12 week supplementation with 1.1 g EPA + 0.8 g DHA/day or corn oil. The composition of FA in the total lipid extract (TLE) of AT from 37 normal weight and 44 obese subjects was assessed by gas chromatography (GC) and the concentration of lipid mediators in AT TLE of 36 normal weight and 45 obese subjects by coupled GC-mass spectrometry.Results:AT of obese subjects had higher concentrations of arachidonic acid (AA), EPA, DPA, PGF2α, arachidonoylethanolamine (AEA), and eicosapentaenoylethanolamine (EPEA) than that of normal weight subjects (P < 0.05). Obese subjects also had and lower concentrations of mediators derived from linoleic and α-linolenic acids, DHA-derived mediators including RvD2 and hydroxydocosahexaenoic acids (HDHAs), AA-derived mediators including lipoxin-B4, hepoxilin-A3, 11,12-dihydroxyeicosatetrienoic acid (DHET), and 6-keto-PGF1α, and the FA ethanolamine of myristic acid and glycerol ester of palmitic acid (P < 0.05 all) than normal weight subjects.Chronic supplementation with EPA + DHA increased the concentration of EPA (P = 0.006) and EPA-derived lipid mediators including dihydroxyeicosatetrienoic acids, EPEA, and EPA-glycerol ester (P < 0.05), and increased the concentration of DHA (P < 0.001), docosahexaenoylethanolamine, and 8-, 11-, 14-, and 16-HDHA (P < 0.05). Chronic supplementation with EPA + DHA also decreased the concentration 4-, 17-, and 20-HDHA, and AA-derived lipid mediators including DHETs, AEA, and LTs in normal weight subjects (P < 0.05), and decreased 2-AG in obese subjects (P < 0.05).Discussion:These data indicate altered lipid signalling in AT in obesity (at baseline) suggesting dysregulation of adipose tissue expansion and inflammatory signalling, including lack of self-resolution, as well as dysregulation in the utilization of supplementary EPA + DHA for synthesis of anti-inflammatory lipid mediators. EPA + DHA are able to modulate synthesis of EPA-, DHA- and AA-derived lipid mediators but obesity may involve resistance to these effects particularly in endocannabinoid synthesis.


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