Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated Fatty Acids in COVID-19: Rationale for the COVID-Omega-F Trial

Arnardottir, Hildur; Pawelzik, Sven-Christian; Wistbacka, Ulf Öhlund; Artiach, Gonzalo; Hofmann, Robin; Reinholdsson, Ingalill; Braunschweig, Frieder; Tornvall, Per; Religa, Dorota; Bäck, Magnus

doi:10.3389/fphys.2020.624657

Cited by 63 publications

(77 citation statements)

References 47 publications

(48 reference statements)

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“…On another level, there is still the question of whether fish oils can raise the levels of SPM levels upon ingestion and in response to acute inflammation in humans ( 63 ). Currently, Karolinska University Hospital is running a trial that will measure the levels of SPM as a secondary outcome following intravenous supplementation of n-3 PUFAs in hospitalized COVID-19 patients to determine whether n-3 PUFAs provide therapeutic value ( 64 , 65 ). Therefore, while this mechanism provides theoretical support for a role for n-3 PUFAs against COVID-19, experimental support is still needed.…”

Section: N-3 Pufamentioning

confidence: 99%

Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment

2021

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Coronavirus disease 2019 (COVID-19) has caused global disruption and a significant loss of life. Existing treatments that can be repurposed as prophylactic and therapeutic agents may reduce the pandemic’s devastation. Emerging evidence of potential applications in other therapeutic contexts has led to the investigation of dietary supplements and nutraceuticals for COVID-19. Such products include vitamin C, vitamin D, omega 3 polyunsaturated fatty acids, probiotics, and zinc, all of which are currently under clinical investigation. In this review, we critically appraise the evidence surrounding dietary supplements and nutraceuticals for the prophylaxis and treatment of COVID-19. Overall, further study is required before evidence-based recommendations can be formulated, but nutritional status plays a significant role in patient outcomes, and these products may help alleviate deficiencies. For example, evidence indicates that vitamin D deficiency may be associated with a greater incidence of infection and severity of COVID-19, suggesting that vitamin D supplementation may hold prophylactic or therapeutic value. A growing number of scientific organizations are now considering recommending vitamin D supplementation to those at high risk of COVID-19. Because research in vitamin D and other nutraceuticals and supplements is preliminary, here we evaluate the extent to which these nutraceutical and dietary supplements hold potential in the COVID-19 crisis. IMPORTANCE Sales of dietary supplements and nutraceuticals have increased during the pandemic due to their perceived “immune-boosting” effects. However, little is known about the efficacy of these dietary supplements and nutraceuticals against the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) or the disease that it causes, CoV disease 2019 (COVID-19). This review provides a critical overview of the potential prophylactic and therapeutic value of various dietary supplements and nutraceuticals from the evidence available to date. These include vitamin C, vitamin D, and zinc, which are often perceived by the public as treating respiratory infections or supporting immune health. Consumers need to be aware of misinformation and false promises surrounding some supplements, which may be subject to limited regulation by authorities. However, considerably more research is required to determine whether dietary supplements and nutraceuticals exhibit prophylactic and therapeutic value against SARS-CoV-2 infection and COVID-19. This review provides perspective on which nutraceuticals and supplements are involved in biological processes that are relevant to recovery from or prevention of COVID-19.

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Section: N-3 Pufamentioning

confidence: 99%

Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment

2021

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“…Thus, increasing omega-3 PUFA and decreasing omega-6 PUFA levels may represent a possible mean to skew the immune response toward resolution of inflammation, which led to the conception of the COVID-Omega-F Trial with the aim of resolving the cytokine storm in COVID-19 patients by supplementation of hospitalized patients with high-dose omega-3 PUFA i.v. over 5 days ( Arnardottir et al, 2021 ), ClinicalTrials.gov Identifier: NCT04647604, estimated study termination date April 30, 2021. However, the situation seems more complex than a simplified omega-3/omega-6 classification would reflect.…”

Section: Bioactive Lipid Mediators In Virus Infection From Influenza Virus To Sars-cov-2mentioning

confidence: 99%

“…While IV emulsions with DHA and EPA were shown to be protective ( Pontes-Arruda and Hirasawa, 2011 ), dietary supplementation with fishoil or with n-3 fatty acids, γ -linolenic acid, and antioxidants did not show a clear benefit in ARDS ( Rice et al, 2011 ; Stapleton et al, 2011 ). On the other hand, independent meta-analyses indicated that supplementation with omega-3 PUFA in patients with ARDS would associate with improvements in the PaO2/FiO2 ratio, with a shorter ICU stay, a shorter duration of mechanical ventilation, and a trend toward reduced mortality ( Dushianthan et al, 2019 ; Langlois et al, 2019 ; Arnardottir et al, 2021 ).…”

Section: Bioactive Lipid Mediators In Virus Infection From Influenza Virus To Sars-cov-2mentioning

confidence: 99%

The Role of Innate Immunity and Bioactive Lipid Mediators in COVID-19 and Influenza

et al. 2021

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In this review, we discuss spatiotemporal kinetics and inflammatory signatures of innate immune cells specifically found in response to SARS-CoV-2 compared to influenza virus infection. Importantly, we cover the current understanding on the mechanisms by which SARS-CoV-2 may fail to engage a coordinated type I response and instead may lead to exaggerated inflammation and death. This knowledge is central for the understanding of available data on specialized pro-resolving lipid mediators in severe SARS-CoV-2 infection pointing toward inhibited E-series resolvin synthesis in severe cases. By investigating a publicly available RNA-seq database of bronchoalveolar lavage cells from patients affected by COVID-19, we moreover offer insights into the regulation of key enzymes involved in lipid mediator synthesis, critically complementing the current knowledge about the mediator lipidome in severely affected patients. This review finally discusses different potential approaches to sustain the synthesis of 3-PUFA-derived pro-resolving lipid mediators, including resolvins and lipoxins, which may critically aid in the prevention of acute lung injury and death from COVID-19.

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“…Notably, the inverse associations between the O3I with the outcome variables were observed within a relatively narrow range of O3I values, which strongly suggests that COVID-19 risk stratification based on O3I categories may indeed be feasible [26]. This finding also reinforces the need to include the basal O3I of eligible participants in future randomized clinical trials of Omega-3 fatty acids in COVID-19 [30][31][32]; unbiased research requires valid comparisons, and the predictive value of biomarkers should be validated in well-designed prospective clinical studies. Increasing evidence strongly suggests the omega-6:Omega-3 fatty acid ratio should be replaced by a metric that focuses on the primary deficiency in Western diets-the lack of EPA and DHA [33]; namely, the Omega-3 Index.…”

Section: Discussionmentioning

confidence: 61%

Omega-3 Index and Clinical Outcomes of Severe COVID-19: Preliminary Results of a Cross-Sectional Study

Müller

Vásquez

et al. 2021

IJERPH

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The potentially detrimental effects of the worldwide deficiency of Omega-3 fatty acids on the COVID-19 pandemic have been underestimated. The Omega-3 Index (O3I), clinical variables, biometric indices, and nutritional information were directly determined for 74 patients with severe COVID-19 and 10 healthy quality-control subjects. The relationships between the OI3 and mechanical ventilation (MV) and death were analyzed. Results: Patients with COVID-19 exhibited low O3I (mean: 4.15%; range: 3.06–6.14%)—consistent with insufficient fish and Omega-3 supplement consumption, and markedly lower than the healthy control subjects (mean: 7.84%; range: 4.65–10.71%). Inverse associations were observed between O3I and MV (OR = 0.459; C.I.: 0.211–0.997) and death (OR = 0.28; C.I.: 0.08–0.985) in severe COVID-19, even after adjusting for sex, age, and well-known risk factors. Conclusion: We present preliminary evidence to support the hypothesis that the risk of severe COVID-19 can be stratified by the O3I quartile. Further investigations are needed to assess the value of the O3I as a blood marker for COVID-19.

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Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated Fatty Acids in COVID-19: Rationale for the COVID-Omega-F Trial

Cited by 63 publications

References 47 publications

Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment

Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment

The Role of Innate Immunity and Bioactive Lipid Mediators in COVID-19 and Influenza

Omega-3 Index and Clinical Outcomes of Severe COVID-19: Preliminary Results of a Cross-Sectional Study

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