The highly infectious coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a new coronavirus that has been spreading since late 2019 and has caused millions of deaths worldwide. COVID-19 continues to spread rapidly worldwide despite high vaccination coverage; therefore, it is crucial to focus on prevention. Most patients experience only mild symptoms of COVID-19. However, in some cases, serious complications can develop mainly due to an exaggerated immune response; that is, a so-called cytokine storm, which can lead to acute respiratory distress syndrome, organ failure, or, in the worst cases, death. N-3 polyunsaturated fatty acids and their metabolites can modulate inflammatory responses, thus reducing the over-release of cytokines. It has been hypothesized that supplementation of n-3 polyunsaturated fatty acids could improve clinical outcomes in critically ill COVID-19 patients. Some clinical trials have shown that administering n-3 polyunsaturated fatty acids to critically ill patients can improve their health and shorten the duration of their stay in intensive care. However, previous clinical studies have some limitations; therefore, further studies are required to confirm these findings.

Department of Human Nutrition and Dietetics Faculty of Food Technology The University of Agriculture in Krakow Krakow Poland

Department of Microbiology Nutrition and Dietetics Faculty of Agrobiology Food and Natural Resources Czech University of Life Sciences Prague Prague Czechia

Zobrazit více v PubMed

Messina G, Polito R, Monda V, Cipolloni L, Di Nunno N, Di Mizio G, et al. . Functional role of dietary intervention to improve the outcome of covid-19: A hypothesis of work. Int J Mol Sci (2020) 21(9):1–14. doi: 10.3390/ijms21093104 PubMed DOI PMC

Shakoor H, Feehan J, Al Dhaheri AS, Ali HI, Platat C, Ismail LC, et al. . Immune-boosting role of vitamins d, c, e, zinc, selenium and omega-3 fatty acids: Could they help against covid-19? Maturitas (2021) 143:1–9. doi: 10.1016/j.maturitas.2020.08.003 PubMed DOI PMC

Darwesh AM, Bassiouni W, Sosnowski DK, Seubert JM. Can n-3 polyunsaturated fatty acids be considered a potential adjuvant therapy for covid-19-associated cardiovascular complications? Pharmacol Ther (2021) 219:107703. doi: 10.1016/j.pharmthera.2020.107703 PubMed DOI PMC

Alimohamadi Y, Sepandi M, Taghdir M, Hosamirudsari H. Determine the most common clinical symptoms in covid-19 patients: A systematic review and meta-analysis. J Prev Med Hyg (2020) 61(3):E304–e12. doi: 10.15167/2421-4248/jpmh2020.61.3.1530 PubMed DOI PMC

Chan AT, Brownstein JS. Putting the public back in public health - surveying symptoms of covid-19. N Engl J Med (2020) 383(7):e45. doi: 10.1056/NEJMp2016259 PubMed DOI

Rocke J, Hopkins C, Philpott C, Kumar N. Is loss of sense of smell a diagnostic marker in covid-19: A systematic review and meta-analysis. Clin otolaryngology Clin Otolaryngol (2020) 45(6):914–22. doi: 10.1111/coa.13620 PubMed DOI PMC

Asher A, Tintle NL, Myers M, Lockshon L, Bacareza H, Harris WS. Blood omega-3 fatty acids and death from covid-19: A pilot study. Prostaglandins Leukot Essent Fatty Acids (2021) 166:102250. doi: 10.1016/j.plefa.2021.102250 PubMed DOI PMC

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, China: A descriptive study. Lancet (2020) 395(10223):507–13. doi: 10.1016/s0140-6736(20)30211-7 PubMed DOI PMC

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. . Clinical Features of patients infected with 2019 novel coronavirus in wuhan, China. Lancet (2020) 395:497–506. doi: 10.1016/S0140-6736(20)30183-5 PubMed DOI PMC

Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. . Association of cardiac injury with mortality in hospitalized patients with covid-19 in Wuhan, China. JAMA Cardiol (2020) 5(7):802–10. doi: 10.1001/jamacardio.2020.0950 PubMed DOI PMC

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. . Clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, China: A retrospective cohort study. Lancet (2020) 395:1054–62. doi: 10.1016/S0140-6736(20)30566-3 PubMed DOI PMC

Matricardi PM, Dal Negro RW, Nisini R. The first, holistic immunological model of covid-19: implications for prevention, diagnosis, and public health measures. Pediatr Allergy Immunol (2020) 31(5):454–70. doi: 10.1111/pai.13271 PubMed DOI PMC

Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe covid-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents (2020) 55(5):105954. doi: 10.1016/j.ijantimicag.2020.105954 PubMed DOI PMC

McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including interleukin-6 in covid-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev (2020) 19(6):102537. doi: 10.1016/j.autrev.2020.102537 PubMed DOI PMC

Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of covid-19 progression. Med Mal Infect (2020) 50(4):382–3. doi: 10.1016/j.medmal.2020.04.002 PubMed DOI PMC

Calder PC. Nutrition and immunity: Lessons for covid-19. Nutr Diabetes (2021) 11(1):1–8. doi: 10.1038/s41387-021-00165-0 PubMed DOI PMC

Calder PC. Nutrition, immunity and covid-19. BMJ Nutr Prev Health (2020) 3(1):74. doi: 10.1136/bmjnph-2020-000085 PubMed DOI PMC

Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta (2015) 1851(4):469–84. doi: 10.1016/j.bbalip.2014.08.010 PubMed DOI

Langlois PL, D'Aragon F, Hardy G, Manzanares W. Omega-3 polyunsaturated fatty acids in critically ill patients with acute respiratory distress syndrome: a systematic review and meta-analysis. Nutrition (2019) 61:84–92. doi: 10.1016/j.nut.2018.10.026 PubMed DOI PMC

Husson MO, Ley D, Portal C, Gottrand M, Hueso T, Desseyn JL, et al. . Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids. J Infect (2016) 73(6):523–35. doi: 10.1016/j.jinf.2016.10.001 PubMed DOI

Weill P, Plissonneau C, Legrand P, Rioux V, Thibault R. May omega-3 fatty acid dietary supplementation help reduce severe complications in covid-19 patients? Biochimie (2020) 179:275–80. doi: 10.1016/j.biochi.2020.09.003 PubMed DOI PMC

Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in covid-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev (2020) 53:25–32. doi: 10.1016/j.cytogfr.2020.05.003 PubMed DOI PMC

Fehr AR, Perlman S. Coronaviruses: An overview of their replication and pathogenesis. Methods Mol Biol (2015) 1282:1–23. doi: 10.1007/978-1-4939-2438-7_1 PubMed DOI PMC

Peiris JS, Yuen KY, Osterhaus AD, Stöhr K. The severe acute respiratory syndrome. N Engl J Med (2003) 349(25):2431–41. doi: 10.1056/NEJMra032498 PubMed DOI

Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med (2012) 367(19):1814–20. doi: 10.1056/NEJMoa1211721 PubMed DOI

Zhou H, Yang J, Zhou C, Chen B, Fang H, Chen S, et al. . A review of SARS-CoV2: Compared with SARS-CoV and MERS-CoV. Front Med (2021) 8:628370. doi: 10.3389/fmed.2021.628370 PubMed DOI PMC

Hathaway D, Pandav K, Patel M, Riva-Moscoso A, Singh BM, Patel A, et al. . Omega 3 fatty acids and covid-19: a comprehensive review. Infect Chemother (2020) 52(4):478–95. doi: 10.3947/ic.2020.52.4.478 PubMed DOI PMC

Abdelrahman Z, Li M, Wang X. Comparative review of SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza a respiratory viruses. Front Immunol (2020) 11:552909. doi: 10.3389/fimmu.2020.552909 PubMed DOI PMC

Baharoon S, Memish ZA. MERS-CoV as an emerging respiratory illness: a review of prevention methods. Travel Med Infect Dis (2019) 32:101520. doi: 10.1016/j.tmaid.2019.101520 PubMed DOI PMC

Weiss SR, Leibowitz JL. Chapter 4 - coronavirus pathogenesis. In: Maramorosch K, Shatkin AJ, Murphy FA, editors. Advances in virus research. Cambridge, Massachusetts: Academic Press; (2011) 81:85–164. PubMed PMC

Glende J, Schwegmann-Wessels C, Al-Falah M, Pfefferle S, Qu X, Deng H, et al. . Importance of cholesterol-rich membrane microdomains in the interaction of the s protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2. Virology (2008) 381(2):215–21. doi: 10.1016/j.virol.2008.08.026 PubMed DOI PMC

Biswas C. Chapter 18 - inflammation in systemic immune diseases: Role of Tlr9 signaling and the resultant oxidative stress in pathology of lupus. In: Chatterjee S, Jungraithmayr W, Bagchi D, editors. Immunity and inflammation in health and disease. Cambridge, Massachusetts: Academic Press; (2018). p. 223–37.

Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. . Cryo-em structure of the 2019-nCoV spike in the prefusion conformation. Science (2020) 367(6483):1260–3. doi: 10.1126/science.abb2507 PubMed DOI PMC

Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell (2020) 181(2):281–92.e6. doi: 10.1016/j.cell.2020.02.058 PubMed DOI PMC

Mahmoud IS, Jarrar YB, Alshaer W, Ismail S. Sars-Cov-2 entry in host cells-multiple targets for treatment and prevention. Biochimie (2020) 175:93–8. doi: 10.1016/j.biochi.2020.05.012 PubMed DOI PMC

van der Poll T, Opal SM. Host-pathogen interactions in sepsis. Lancet Infect Dis (2008) 8(1):32–43. doi: 10.1016/s1473-3099(07)70265-7 PubMed DOI

Asehnoune K, Villadangos J, Hotchkiss RS. Understanding host-pathogen interaction. Intensive Care Med (2016) 42(12):2084–6. doi: 10.1007/s00134-016-4544-8 PubMed DOI

Zhang X-J, Qin J-J, Cheng X, Shen L, Zhao Y-C, Yuan Y, et al. . In-hospital use of statins is associated with a reduced risk of mortality among individuals with covid-19. Cell Metab (2020) 32(2):176–87.e4. doi: 10.1016/j.cmet.2020.06.015 PubMed DOI PMC

Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, et al. . Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-Infected mice. Cell Host Microbe (2016) 19(2):181–93. doi: 10.1016/j.chom.2016.01.007 PubMed DOI PMC

Eppensteiner J, Kwun J, Scheuermann U, Barbas A, Limkakeng AT, Kuchibhatla M, et al. . Damage- and pathogen-associated molecular patterns play differential roles in late mortality after critical illness. JCI Insight (2019) 4(16):e127925. doi: 10.1172/jci.insight.127925 PubMed DOI PMC

Nicholls JM, Poon LL, Lee KC, Ng WF, Lai ST, Leung CY, et al. . Lung pathology of fatal severe acute respiratory syndrome. Lancet (2003) 361(9371):1773–8. doi: 10.1016/s0140-6736(03)13413-7 PubMed DOI PMC

Li C, He Q, Qian H, Liu J. Overview of the pathogenesis of covid-19 (Review). Exp Ther Med (2021) 22(3):1011. doi: 10.3892/etm.2021.10444 PubMed DOI PMC

Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. . Coronavirus infections and immune responses. J Med Virol (2020) 92(4):424–32. doi: 10.1002/jmv.25685 PubMed DOI PMC

Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost (2020) 18(6):1421–4. doi: 10.1111/jth.14830 PubMed DOI PMC

Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost (2020) 18(5):1094–9. doi: 10.1111/jth.14817 PubMed DOI PMC

Han H, Yang L, Liu R, Liu F, Wu KL, Li J, et al. . Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med (2020) 58(7):1116–20. doi: 10.1515/cclm-2020-0188 PubMed DOI

Liu D, Wang Q, Zhang H, Cui L, Shen F, Chen Y, et al. . Viral sepsis is a complication in patients with novel corona virus disease (Covid-19). Med Drug Discovery (2020) 8:100057. doi: 10.1016/j.medidd.2020.100057 PubMed DOI PMC

Elezkurtaj S, Greuel S, Ihlow J, Michaelis EG, Bischoff P, Kunze CA, et al. . Causes of death and comorbidities in hospitalized patients with covid-19. Sci Rep (2021) 11(1):4263. doi: 10.1038/s41598-021-82862-5 PubMed DOI PMC

Wang K, Qiu Z, Liu J, Fan T, Liu C, Tian P, et al. . Analysis of the clinical characteristics of 77 covid-19 deaths. Sci Rep (2020) 10(1):16384. doi: 10.1038/s41598-020-73136-7 PubMed DOI PMC

Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, et al. . Induction of pro-inflammatory cytokines (Il-1 and il-6) and lung inflammation by coronavirus-19 (Covi-19 or SARS-CoV-2): Anti-inflammatory strategies. J Biol Regul Homeost (2020) 34(2):327–31. doi: 10.23812/conti-e PubMed DOI

Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. . The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (Covid-19): The perspectives of clinical immunologists from China. Clin Immunol (2020) 214:108393–. doi: 10.1016/j.clim.2020.108393 PubMed DOI PMC

Jump DB. The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem (2002) 277(11):8755–8. doi: 10.1074/jbc.R100062200 PubMed DOI

Burdge GC, Calder PC. Introduction to fatty acids and lipids. World Rev Nutr Diet (2015) 112:1–16. doi: 10.1159/000365423 PubMed DOI

Schuchardt JP, Hahn A. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids (2013) 89(1):1–8. doi: 10.1016/j.plefa.2013.03.010 PubMed DOI

Siriwardhana N, Kalupahana NS, Moustaid-Moussa N. Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and docosahexaenoic acid. Adv Food Nutr Res (2012) 65:211–22. doi: 10.1016/b978-0-12-416003-3.00013-5 PubMed DOI

Baker EJ, Valenzuela CA, De Souza CO, Yaqoob P, Miles EA, Calder PC. Comparative anti-inflammatory effects of plant- and marine-derived omega-3 fatty acids explored in an endothelial cell line. Biochim Biophys Acta - Mol Cell Biol Lipids. (2020) 1865(6):158662. doi: 10.1016/j.bbalip.2020.158662 PubMed DOI

EFSA Panel on Dietetic Products N, Allergies . Scientific opinion on dietary reference values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA J (2010) 8(3):1461. doi: 10.2903/j.efsa.2010.1461 DOI

EFSA Panel on Dietetic Products N, Allergies . Scientific opinion on nutrient requirements and dietary intakes of infants and young children in the european union. EFSA J (2013) 11(10):3408. doi: 10.2903/j.efsa.2013.3408 DOI

Nutrition EPoDP, Allergies . Dietary reference values for nutrients. Summary Rep EFSA Supporting Publ (2017) 2017:e15121. doi: 10.2903/sp.efsa.2017.e15121 DOI

Joint F. A. O. Fats and fatty acids in human nutrition. report of an expert consultation. Geneva. (2010) 10–14. PubMed

Sioen I, van Lieshout L, Eilander A, Fleith M, Lohner S, Szommer A, et al. . Systematic review on n-3 and n-6 pufa intake in european countries in light of the current recommendations–focus on specific population groups. Ann Nutr Metab (2017) 70(1):39–50. doi: 10.1159/000456723 PubMed DOI PMC

Papanikolaou Y, Brooks J, Reider C, Fulgoni VL, 3rd. U.S. adults are not meeting recommended levels for fish and omega-3 fatty acid intake: results of an analysis using observational data from nhanes 2003-2008. Nutr J (2014) 13:31. doi: 10.1186/1475-2891-13-31 PubMed DOI PMC

Harton A, Choroszewska A, Gajewska D, Myszkowska-Ryciak J. Intake of polyunsaturated fatty acids by pregnant women. Probl Hig Epidemiol (2013) 94(3):605–9.

Nowacka E, Kopeć A, Leszczyńska T, Polaszczyk S, Pysz K. Total fats and fatty acids consumption by sportsmen practicing slalom canoe and sport-shooting. Sci Sports (2013) 28(3):e41–50. doi: 10.1016/j.scispo.2012.07.002 DOI

Bentsen H. Dietary polyunsaturated fatty acids, brain function and mental health. Microb Ecol Health Dis (2017) 28(sup1):1281916. doi: 10.1080/16512235.2017.1281916 DOI

McClaskey EM, Michalets EL. Subdural hematoma after a fall in an elderly patient taking high-dose omega-3 fatty acids with warfarin and aspirin: case report and review of the literature. Pharmacotherapy (2007) 27(1):152–60. doi: 10.1592/phco.27.1.152 PubMed DOI

Wassall SR, Leng X, Canner SW, Pennington ER, Kinnun JJ, Cavazos AT, et al. . Docosahexaenoic acid regulates the formation of lipid rafts: A unified view from experiment and simulation. Biochim Biophys Acta Biomembr (2018) 1860(10):1985–93. doi: 10.1016/j.bbamem.2018.04.016 PubMed DOI PMC

Pérez-Torres I, Guarner-Lans V, Soria-Castro E, Manzano-Pech L, Palacios-Chavarría A, Valdez-Vázquez RR, et al. . Alteration in the lipid profile and the desaturases activity in patients with severe pneumonia by SARS-CoV-2. Front Physiol (2021) 12:667024. doi: 10.3389/fphys.2021.667024 PubMed DOI PMC

Kang KW, Kim S, Cho YB, Ryu SR, Seo YJ, Lee SM. Endogenous n-3 polyunsaturated fatty acids are beneficial to dampen CD8(+) T cell-mediated inflammatory response upon the viral infection in mice. Int J Mol Sci (2019) 20(18):1–11. doi: 10.3390/ijms20184510 PubMed DOI PMC

Yuan S, Chu H, Chan JF, Ye ZW, Wen L, Yan B, et al. . Srebp-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Nat Commun (2019) 10(1):120. doi: 10.1038/s41467-018-08015-x PubMed DOI PMC

Bond LM, Miyazaki M, O’Neill LM, Ding F, Ntambi JM. Chapter 6 - fatty acid desaturation and elongation in mammals. In: Ridgway ND, McLeod RS, editors. Biochemistry of lipids, lipoproteins and membranes, Sixth Edition. Boston: Elsevier; (2016). p. 185–208.

Bayly GR. Chapter 37 - lipids and disorders of lipoprotein metabolism. In: Marshall WJ, Lapsley M, Day AP, Ayling RM, editors. Clinical biochemistry: Metabolic and clinical aspects, 3rd ed. London: Churchill Livingstone; (2014). p. 702–36.

Deckelbaum RJ, Worgall TS, Seo T. N-3 fatty acids and gene expression. Am J Clin Nutr (2006) 83(6 Suppl):1520s–5s. doi: 10.1093/ajcn/83.6.1520S PubMed DOI

Horton JD, Goldstein JL, Brown MS. Srebps: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest (2002) 109(9):1125–31. doi: 10.1172/jci15593 PubMed DOI PMC

Thewke DP, Panini SR, Sinensky M. Oleate potentiates oxysterol inhibition of transcription from sterol regulatory element-1-regulated promoters and maturation of sterol regulatory element-binding proteins. J Biol Chem (1998) 273(33):21402–7. doi: 10.1074/jbc.273.33.21402 PubMed DOI

Worgall TS, Sturley SL, Seo T, Osborne TF, Deckelbaum RJ. Polyunsaturated fatty acids decrease expression of promoters with sterol regulatory elements by decreasing levels of mature sterol regulatory element-binding protein. J Biol Chem (1998) 273(40):25537–40. doi: 10.1074/jbc.273.40.25537 PubMed DOI

Hannah VC, Ou J, Luong A, Goldstein JL, Brown MS. Unsaturated fatty acids down-regulate srebp isoforms 1a and 1c by two mechanisms in HEK-293 cells. J Biol Chem (2001) 276(6):4365–72. doi: 10.1074/jbc.M007273200 PubMed DOI

Johnson RA, Hamilton JA, Worgall TS, Deckelbaum RJ. Free fatty acids modulate intermembrane trafficking of cholesterol by increasing lipid mobilities: novel 13c NMR analyses of free cholesterol partitioning. Biochem. (2003) 42(6):1637–45. doi: 10.1021/bi0264465 PubMed DOI

Worgall TS, Johnson RA, Seo T, Gierens H, Deckelbaum RJ. Unsaturated fatty acid-mediated decreases in sterol regulatory element-mediated gene transcription are linked to cellular sphingolipid metabolism. J Biol Chem (2002) 277(6):3878–85. doi: 10.1074/jbc.M102393200 PubMed DOI

Rosenwald AG, Machamer CE, Pagano RE. Effects of a sphingolipid synthesis inhibitor on membrane transport through the secretory pathway. Biochem. (1992) 31(14):3581–90. doi: 10.1021/bi00129a005 PubMed DOI

Worgall TS, Juliano RA, Seo T, Deckelbaum RJ. Ceramide synthesis correlates with the posttranscriptional regulation of the sterol-regulatory element-binding protein. Arterioscler Thromb Vasc Biol (2004) 24(5):943–8. doi: 10.1161/01.atv.0000125703.20434.4d PubMed DOI

Innes JK, Calder PC. Marine omega-3 (n-3) fatty acids for cardiovascular health: an update for 2020. Int J Mol Sci (2020) 21(4):1362. doi: 10.3390/ijms21041362 PubMed DOI PMC

Dennis EA, Norris PC. Eicosanoid storm in infection and inflammation. Nat Rev Immunol (2015) 15(8):511–23. doi: 10.1038/nri3859 PubMed DOI PMC

Harizi H, Corcuff JB, Gualde N. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol Med (2008) 14(10):461–9. doi: 10.1016/j.molmed.2008.08.005 PubMed DOI

Gerling CJ, Mukai K, Chabowski A, Heigenhauser GJF, Holloway GP, Spriet LL, et al. . Incorporation of omega-3 fatty acids into human skeletal muscle sarcolemmal and mitochondrial membranes following 12 weeks of fish oil supplementation. Front Physiol (2019) 10:348. doi: 10.3389/fphys.2019.00348 PubMed DOI PMC

Serhan CN, Dalli J, Colas RA, Winkler JW, Chiang N. Protectins and maresins: new pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome. Biochim Biophys Acta - Mol Cell Biol Lipids. (2015) 1851(4):397–413. doi: 10.1016/j.bbalip.2014.08.006 PubMed DOI PMC

Regidor PA, Santos FG, Rizo JM, Egea FM. Pro resolving inflammatory effects of the lipid mediators of omega 3 fatty acids and its implication in SARS covid-19. Med Hypotheses (2020) 145:110340. doi: 10.1016/j.mehy.2020.110340 PubMed DOI PMC

Basil MC, Levy BD. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol (2016) 16(1):51–67. doi: 10.1038/nri.2015.4 PubMed DOI PMC

Serhan CN, Gotlinger K, Hong S, Arita M. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: An overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat (2004) 73(3-4):155–72. doi: 10.1016/j.prostaglandins.2004.03.005 PubMed DOI

Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol (2008) 8(5):349–61. doi: 10.1038/nri2294 PubMed DOI PMC

Rius B, López-Vicario C, González-Périz A, Morán-Salvador E, García-Alonso V, Clária J, et al. . Resolution of inflammation in obesity-induced liver disease. Front Immunol (2012) 3:257. doi: 10.3389/fimmu.2012.00257 PubMed DOI PMC

Schulze MB, Minihane AM, Saleh RNM, Risérus U. Intake and metabolism of omega-3 and omega-6 polyunsaturated fatty acids: nutritional implications for cardiometabolic diseases. Lancet Diabetes Endocrinol (2020) 8(11):915–30. doi: 10.1016/s2213-8587(20)30148-0 PubMed DOI

Souza DR, Pieri B, Comim VH, Marques SO, Luciano TF, Rodrigues MS, et al. . Fish oil reduces subclinical inflammation, insulin resistance, and atherogenic factors in overweight/obese type 2 diabetes mellitus patients: A pre-post pilot study. J Diabetes Complicat (2020) 34(5):107553. doi: 10.1016/j.jdiacomp.2020.107553 PubMed DOI

Malekshahi Moghadam A, Saedisomeolia A, Djalali M, Djazayery A, Pooya S, Sojoudi F. Efficacy of omega-3 fatty acid supplementation on serum levels of tumour necrosis factor-alpha, c-reactive protein and interleukin-2 in type 2 diabetes mellitus patients. Singap Med J (2012) 53(9):615–9. PubMed

Tan A, Sullenbarger B, Prakash R, McDaniel JC. Supplementation with eicosapentaenoic acid and docosahexaenoic acid reduces high levels of circulating proinflammatory cytokines in aging adults: A randomized, controlled study. Prostaglandins Leukot Essent Fatty Acids (2018) 132:23–9. doi: 10.1016/j.plefa.2018.03.010 PubMed DOI PMC

Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J, Iwamoto R, et al. . The lipid mediator protectin d1 inhibits influenza virus replication and improves severe influenza. Cell (2013) 153(1):112–25. doi: 10.1016/j.cell.2013.02.027 PubMed DOI

Ramon S, Baker SF, Sahler JM, Kim N, Feldsott EA, Serhan CN, et al. . The specialized proresolving mediator 17-hdha enhances the antibody-mediated immune response against influenza virus: a new class of adjuvant? J Immunol Res (2014) 193(12):6031–40. doi: 10.4049/jimmunol.1302795 PubMed DOI PMC

Braz de Melo H, Nascimento G, Corrêa R, Almeida R, Santos I, Prado P, et al. . Potential neuroprotective and anti-inflammatory effects provided by omega-3 (DHA) against zika virus infection in human SH-SY5Y cells. Sci Rep (2019) 9:20119. doi: 10.1038/s41598-019-56556-y PubMed DOI PMC

Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. . Incidence and outcomes of acute lung injury. N Engl J Med (2005) 353(16):1685–93. doi: 10.1056/NEJMoa050333 PubMed DOI

García de Acilu M, Leal S, Caralt B, Roca O, Sabater J, Masclans JR. The role of omega-3 polyunsaturated fatty acids in the treatment of patients with acute respiratory distress syndrome: a clinical review. BioMed Res Int (2015) 2015:653750. doi: 10.1155/2015/653750 PubMed DOI PMC

Kornecki A, Singh RN. 38 - acute respiratory distress syndrome. In: Wilmott RW, Deterding R, Li A, Ratjen F, Sly P, Zar HJ, et al., editors. Kendig's disorders of the respiratory tract in children, Ninth Edition. Philadelphia: Elsevier; (2019). p. 606–14.e3.

Bakowitz M, Bruns B, McCunn M. Acute lung injury and the acute respiratory distress syndrome in the injured patient. Scand J Trauma Resusc Emerg Med (2012) 20:54. doi: 10.1186/1757-7241-20-54 PubMed DOI PMC

Channappanavar R, Perlman S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin Immunopathol (2017) 39(5):529–39. doi: 10.1007/s00281-017-0629-x PubMed DOI PMC

Hasan SS, Capstick T, Ahmed R, Kow CS, Mazhar F, Merchant HA, et al. . Mortality in covid-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. Expert Rev Respir Med (2020) 14(11):1149–63. doi: 10.1080/17476348.2020.1804365 PubMed DOI PMC

Singer P, Theilla M, Fisher H, Gibstein L, Grozovski E, Cohen J. Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury. Crit Care Med (2006) 34(4):1033–8. doi: 10.1097/01.Ccm.0000206111.23629.0a PubMed DOI

Pontes-Arruda A, Demichele S, Seth A, Singer P. The use of an inflammation-modulating diet in patients with acute lung injury or acute respiratory distress syndrome: A meta-analysis of outcome data. JPEN J Parenter Enteral Nutr (2008) 32(6):596–605. doi: 10.1177/0148607108324203 PubMed DOI

Shirai K, Yoshida S, Matsumaru N, Toyoda I, Ogura S. Effect of enteral diet enriched with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with sepsis-induced acute respiratory distress syndrome. J Intensive Care (2015) 3(1):24. doi: 10.1186/s40560-015-0087-2 PubMed DOI PMC

Parish M, Valiyi F, Hamishehkar H, Sanaie S, Asghari Jafarabadi M, Golzari SE, et al. . The effect of omega-3 fatty acids on ards: A randomized double-blind study. Adv Pharm Bull (2014) 4(Suppl 2):555–61. doi: 10.5681/apb.2014.082 PubMed DOI PMC

Wentowski C, Ingles DP, Nielsen ND. Sepsis 2021: A review. Anaesth Intensive Care Med (2021) 22(11):676–84. doi: 10.1016/j.mpaic.2021.10.001 DOI

Pontes-Arruda A, Aragão AM, Albuquerque JD. Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med (2006) 34(9):2325–33. doi: 10.1097/01.Ccm.0000234033.65657.B6 PubMed DOI

Hosny M, Nahas R, Ali S, Elshafei SA, Khaled H. Impact of oral omega-3 fatty acids supplementation in early sepsis on clinical outcome and immunomodulation. Egypt J Crit Care Med (2013) 1(3):119–26. doi: 10.1016/j.ejccm.2013.11.002 DOI

Chen H, Wang S, Zhao Y, Luo Y, Tong H, Su L. Correlation analysis of omega-3 fatty acids and mortality of sepsis and sepsis-induced ARDS in adults: data from previous randomized controlled trials. Nutr J (2018) 17(1):57. doi: 10.1186/s12937-018-0356-8 PubMed DOI PMC

Wang C, Han D, Feng X, Wu J. Omega-3 fatty acid supplementation is associated with favorable outcomes in patients with sepsis: An updated meta-analysis. Int J Med Res (2020) 48(12):300060520953684. doi: 10.1177/0300060520953684 PubMed DOI PMC

Mo Y, Hu X, Chang L, Ma P. [the effect of Ω-3 fatty acid supplementation in parenteral nutrition on the outcome of patients with sepsis: A systematic review and meta-analysis]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue (2014) 26(3):142–7. doi: 10.3760/cma.j.issn.2095-4352.2014.03.004 PubMed DOI

Doaei S, Gholami S, Rastgoo S, Gholamalizadeh M, Bourbour F, Bagheri SE, et al. . The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with covid-19: A randomized clinical trial. J Transl Med (2021) 19(1):128. doi: 10.1186/s12967-021-02795-5 PubMed DOI PMC

Sedighiyan M, Abdollahi H, Karimi E, Badeli M, Erfanian R, Raeesi S, et al. . Omega-3 polyunsaturated fatty acids supplementation improve clinical symptoms in patients with covid-19: A randomised clinical trial. Int J Clin Pract (2021) 75(12):e14854. doi: 10.1111/ijcp.14854 PubMed DOI

AG SP . A randomised, double-blind, placebo controlled study of eicosapentaenoic acid (EPA-FFA) gastro-resistant capsules to treat hospitalised subjects with confirmed SARS-CoV-2. (2020). Available at: https://clinicaltrials.gov/ct2/show/NCT04335032

Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol (2013) 75(3):645–62. doi: 10.1111/j.1365-2125.2012.04374.x PubMed DOI PMC

Bistrian BR. Parenteral fish-oil emulsions in critically ill covid-19 emulsions. JPEN J Parenter Enteral Nutr (2020) 44(7):1168. doi: 10.1002/jpen.1871 PubMed DOI PMC

Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, et al. . The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med (1989) 320(5):265–71. doi: 10.1056/nejm198902023200501 PubMed DOI

Waitzberg DL, Torrinhas RS. Fish oil lipid emulsions and immune response: what clinicians need to know. Nutr Clin Pract (2009) 24(4):487–99. doi: 10.1177/0884533609339071 PubMed DOI