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High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia.

ABSTRACT: COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19.Trial registration: NCT04435223.

SUBMITTER: Nguyen M

PROVIDER: S-EPMC8144366 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia.

Nguyen Maxime M Bourredjem Abderrahmane A Piroth Lionel L Bouhemad Bélaïd B Jalil Antoine A Pallot Gaetan G Le Guern Naig N Thomas Charles C Pilot Thomas T Bergas Victoria V Choubley Hélène H Quenot Jean-Pierre JP Charles Pierre-Emmanuel PE Lagrost Laurent L Deckert Valerie V de Barros Jean-Paul Pais JP Guinot Pierre-Grégoire PG Masson David D Binquet Christine C Gautier Thomas T Blot Mathieu M

Scientific reports 20210524 1

COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, li ...[more]

PMID: 34031519

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Project description:BackgroundImmune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia.ObjectiveThis study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan-Kynurenine pathway and the severity of severe pneumonia, as well as N-3/N-6 polyunsaturated fatty acids (PUFAs).MethodsIn this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups.ResultsMetabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (linolenic acid, α-LNA), arachidonic acid (ARA), Dihomo-γ-linolenic acid (DGLA), and 13(s)-hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)-hydroxyeicosatetraenoic acid (HETE), 11(S)-HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)-hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α-LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)-HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α-LNA, DHA, and DPA.ConclusionThis study revealed that during severe pneumonia, the Tryptophan-Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan-Kynurenine pathway was negatively correlated with N-3/N-6 PUFAs.

Project description:BackgroundOmega-3 polyunsaturated fatty acids (PUFAs) were proposed to have potential effects against inflammation and cancer. However, results from epidemiology studies remain inconsistent. We aimed to explore the associations of plasma PUFAs with EC recurrence and all-cause mortality.MethodWomen diagnosed with endometrial cancer (EC) between 2008 and 2013 and underwent surgery at Fudan University Shanghai Cancer Center of China were recruited. Survival status was followed up through September 2017. EC recurrence and total cause deaths were identified through medical record and telephone interview. In total, 202 patients with enough plasma samples at time of surgery were included. There were 195 patients who provided baseline plasma and survival information included in the current study. Plasma omega-3 PUFAs were measured by GC-FID. Cox Proportional Hazard model adjusted for potential cofounders was used to estimate HRs and 95% CIs.ResultsMedian follow-up time for patients was 58 months after surgery. A total of 13 recurrences and 11 all-cause deaths, of which, 2 deaths from EC, were identified. Level of plasma EPA was higher in recurrent patients than total patients (0.78% vs 0.51%, P = 0.015). Higher plasma eicosapentaenoic acid (EPA) level trended to have positive association with EC recurrence (P-trend = 0.04), although comparing to the lowest tertile, the highest tertile of EPA level was not significantly associated with increased risk of EC recurrence (HRT3vsT1 = 6.02; 95%CI = 0.7-52.06). The association between total omega-3 PUFA and EC recurrence tended to be stronger among patients with deeper myometrial invasion (OR = 3.41; 95%CI = 1.06-10.95; P-interaction = 0.04).ConclusionsHigher plasma EPA level was significantly associated with EC recurrence. Further studies are warranted to confirm these findings.Trial registrationChiCTR1900025418; Retrospectively registered (26 August 2019); Chinses Clinical Trial Registry.

Project description:Calves may experience increased oxidative stress at birth through activation of metabolic and respiratory processes. Reducing oxidative stress may enhance calf viability in early life. Our objective was to determine the dose response to fish and flaxseed oil when supplemented in colostrum on concentrations of plasma fatty acid (FA), FA metabolites, and index of oxidative stress during the critical first week of life in calves to understand how supplementing n-3 FA may decrease oxidative stress. We hypothesized that n-3 FA supplemented in colostrum in a linear dose-dependent fashion would associate with increased plasma n-3 FA concentrations and decreased oxidative stress. Twenty-four male and female Holstein calves were randomly assigned to receive 0, 30, 60, or 120 mL of a 1:1 fish to flaxseed oil supplement in colostrum. All calves received 2.8 L of previously frozen colostrum (≥22% Brix) with their respective treatment within 6 h after birth. Blood was sampled before first feeding after birth and on d 1, 2, 4, 7, and 14 d of age to assess oxidant status and plasma free PUFA, phospholipid FA, and oxylipid concentrations. Health indicators were observed daily. Indicators of general health and growth were unaffected by treatment. Supplemented calves exhibited greater concentrations of n-3 FA in plasma as free and phospholipid FA and some n-3 and n-6 FA-derived oxylipids in the first week of life in a linear fashion with increasing supplemental dose. Fish and flaxseed oil treatments did not alter oxidant status but overall decreased isoprostane concentrations in plasma, indicating oxidative stress was decreased. Together, these responses indicate that the fish and flaxseed oil supplement was antiinflammatory. In conclusion, supplementing colostrum with 30, 60, and 120 mL of a 1:1 mixture of fish and flaxseed oil linearly increased plasma concentrations of n-3 FA and metabolites and decreased biomarkers of oxidative stress, but did not alter oxidant status or affect health or growth. Our findings suggest neonatal calves may benefit from n-3 FA supplementation in colostrum to encourage a greater antiinflammatory state.

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High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia.

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High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia.

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