Immunomodulatory meaning of diet and COVID-19
More details
Hide details
Department of Pathophysiology, Collegium Medicum, Jagiellonian University, Kraków, Poland
Dominika Grońska   

Katedra Patofizjologii, Collegium Medicum Uniwersytetu Jagiellońskiego w Krakowie, Czysta 18, 31-121, Kraków, Polska
Introduction and objective:
The latest scientific reports showed that there is a relationship between the state of the gastrointestinal tract and the immune system, and the incidence of COVID-19. Diet can exert an immunomodulatory effect and regulate the immune response of an organism. The aim of the review is to show the effects of immunomodulators contained/supplemented in a diet on the infection SARS-CoV-2 and the course of COVID-19.

Review methods:
The literature review was conducted using PubMed, Google Scholar and the Medline database.

Abbreviated description of the state of knowledge:
Regular vitamin D supplementation significantly reduces the risk of respiratory infection with SARS-CoV-2; vitamin C may inhibit the expression of the ACE2 receptor in human small alveolar epithelial cells and limit the penetration of SARS-CoV-2; reduced iron levels predispose people to severe COVID-19 symptoms; selenium deficiency may be responsible for a decreased level of antibodies and NK cell cytotoxicity. Aloë vera isolated polysaccharides strengthens the immune system; the quercetin and ellagic acid in combination with virus proteins show potential antiviral activity against SARSCoV- 2. Subsequently, adaptogens, ginger, echinacea and curcumin - showed anti-inflammatory effects. Also, the optimal composition of the gut microbiota improved/maintained the integrity of the lymphoid tissue found in the gastrointestinal tract (GALT) and the functioning of the gut-pulmonary axis.

Natural immunomodulators may be a relatively safe therapeutic option in patients during the course of COVID-19, but there are still no official recommendations for their practical use in therapy. It should be emphasized that there is a need for further scientific research into the mechanisms of action and efficacy of phytotherapy in the context of the effectiveness of plant-based immunostimulants in alleviating the course of COVID-19 disease.

Dhar D, Mohanty A. Gut microbiota and Covid-19- possible link and implications. Virus research. 2020; 285: 198018.
Harmer D, Gilbert M, Borman R, et al. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS letters. 2002; 532(1–2): 107–110.
Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017; 9(11): 1211. https://doi. 10.3390/nu9111211.
Dang AT, Marsland BJ. Microbes, metabolites, and the gut-lung axis. Mucosal immunology. 2019; 12(4): 843–850.
Anand S, Mande SS. Diet, Microbiota and Gut-Lung Connection. Frontiers in microbiology. 2018; 9: 2147.
Allali I, Bakri Y, Amzazi S, et al. Gut-Lung Axis in COVID-19. Interdisciplinary perspectives on infectious diseases. 2021; 6655380.
Pisoschi AM, Pop A, Iordache F, et al. Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy. Eur J Med Chem. 2022; 232: 114175. https://doi.10.1016/j.ejmech.2....
Shakoor H, Feehan J, Al Dhaheri AS, 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. https://doi.10.1016/j.maturita....
Razdan K, Singh K, Singh D. Vitamin D Levels and COVID-19 Susceptibility: Is there any Correlation? Med Drug Discov. 2020; 7: 100051. https://doi.10.1016/j.medidd.2....
Lee GY, Han SN. The Role of Vitamin E in Immunity. Nutrients. 2018; 10(11): 1614. https://doi.10.3390/nu10111614.
Zhou YF, Luo BA, Qin LL. The association between vitamin D deficiency and community-acquired pneumonia: A meta-analysis of observational studies. Medicine (Baltimore). 2019; 98(38): 17252. https://doi.10.1097/MD.0000000....
Ramos EM, Araújo ELL, de Souza ID, et al. Vitamin D, Zinc and Iron in Adult Patients with Covid-19 and Their Action in The Immune Response as Biomarkers: A Case Report. Preprints. 2021; 2021050413. https://doi.10.20944/preprints....
Khorasanchi Z, Jafazadeh Esfehani A, Sharifan P, et al. The effects of high dose vitamin D supplementation as a nutritional intervention strategy on biochemical and inflammatory factors in adults with COVID-19: Study protocol for a randomized controlled trial. Nutr Health. 2022; 24: 2601060221082384. https://doi.10.1177/0260106022....
Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017; 9(11): 1213. https://doi. 10.3390/nu9111211.
Hemilä H, Chalker E. Vitamin C as a Possible Therapy for COVID-19. Infect Chemother. 2020; 52(2): 222–223. https://doi.10.3947/ic.2020.52....
Cheng RZ. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)? Med Drug Discov. 2020; 5: 100028. https://doi.10.1016/j.medidd.2....
Carr AC. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Crit Care. 2020; 24(1): 133. https://doi.10.1186/s13054-020....
Bae M, Kim H. Mini-Review on the Roles of Vitamin C, Vitamin D, and Selenium in the Immune System against COVID-19. Molecules. 2020; 25(22): 5346. https://doi.10.3390/molecules2....
Li R, Wu K, Li Y, et al. Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19. Aging (Albany NY). 2020; 12(15): 15784–15796. https://doi.10.18632/aging.103....
Li R, Wu K, Li Y, et al. Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19. Aging (Albany NY). 2020; 12(15): 15784–15797. https://doi.10.18632/aging.103....
Kieliszek M, Lipinski B. Selenium supplementation in the prevention of coronavirus infections (COVID-19). Med Hypotheses. 2020; 143: 109878. https://doi.10.1016/j.mehy.202....
Patel O, Chinni V, El-Khoury J, et al. A pilot double-blind safety and feasibility randomized controlled trial of high-dose intravenous zinc in hospitalized COVID-19 patients. J Med Virol. 2020; 93(5): 3261–3267. https://doi.10.1002/jmv.26895.
Ramos EM, Araújo ELL, de Souza ID, et al. Vitamin D, Zinc and Iron in Adult Patients with Covid-19 and Their Action in The Immune Response as Biomarkers: A Case Report. Preprints. 2021; 2021050414. https://doi.10.20944/preprints....
Dymarska E, Grochowalska A, Krauss H, et al. Natural immune response modifiers. Probl Hig Epidemiol. 2016; 97(4): 297–307.
Asif M, Saleem M, Saadullah M, et al. COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties. Inflammopharmacology. 2020; 28(5): 1153–1161. https://doi.10.1007/s10787-020....
Al-Horani RA, Kar S, Aliter KF. Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials. Int J Mol Sci. 2020; 21(15): 5224. https://doi.10.3390/ijms211552....
Ang L, Lee HW, Kim A, et al. Herbal medicine for the management of COVID-19 during the medical observation period: A review of guidelines. Integr Med Res. 2020; 9(3): 100465. https://doi.10.1016/j.imr.2020....
Boozari M, Hosseinzadeh H. Natural products for COVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies. Phytotherapy Research. 2020; 1–13.
Liang J, Cui L, Li J, et al. Aloe vera: A Medicinal Plant Used in Skin Wound Healing. Tissue Eng Part B Rev. 2021; 27(5): 455–474. https://doi.10.1089/ten.TEB.20....
Roge A, Warwas M. Stężenie polisacharydów a aktywność antyoksydacyjna w preparatach aloesu. Farm Pol. 2010; 66(9): 593–597.
Grace OM, Buerki S, Symonds MR, et al. Evolutionary history and leaf succulence as explanations for medicinal use in aloes and the global popularity of Aloe vera. BMC Evol Biol. 2015; 15: 29. https://doi.10.1186/s12862-015....
Liu C, Cui Y, Pi F, et al. Extraction, Purification, Structural Characteristics, Biological Activities and Pharmacological Applications of Acemannan, a Polysaccharide from Aloe vera: A Review. Molecules. 2019; 24(8): 1554. https://doi.10.3390/molecules2....
Kumar S, Tiku AB. Immunomodulatory potential of acemannan (polysaccharide from Aloe vera) against radiation induced mortality in Swiss albino mice. Food Agric. Immunol. 2016; 27: 72–86.
Lee JK, Lee MK, Yun YP, et al. Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. Int Immunopharmacol. 2001; 1(7): 1275–84. https://doi.10.1016/s1567-5769....
Białas-Chromiec B, Skopińska-Różewska E, Strzelecka H, et al. Immunomodulacyjne właściwości Biostyminy – wodnego wyciągu z liści roślin trzyletnich Aloe arborescens Mill. Onkol Pol. 2000; 3(2): 85–89.
Zhang L, Tizard IR. Activation of a mouse macrophage cell line by acemannan: the major carbohydrate fraction from Aloe vera gel. Immunopharmacology. 1996; 35(2): 119–28. https://doi.10.1016/s0162- 3109(96)00135-x.
Glatthaar-Saalmuller B, Michalak A, Bastian P, et al. Ocena aktywności przeciwwirusowej in vitro preparatów Biostymina i Bioaron C względem ludzkiego Rhinowirusa (HRV14). Post Fitoter. 2012; 3: 156–161.
Borowska S, Brzóska MM. Chokeberries (Aronia melanocarpa) and Their Products as a Possible Means for the Prevention and Treatment of Noncommunicable Diseases and Unfavorable Health Effects Due to Exposure to Xenobiotics. Compr Rev Food Sci Food Saf. 2016; 15(6): 982–1017. https://doi.10.1111/1541-4337.....
Staszowska-Karkut M, Materska M. Phenolic Composition, Mineral Content, and Beneficial Bioactivities of Leaf Extracts from Black Currant (Ribes nigrum L.), Raspberry (Rubus idaeus), and Aronia (Aronia melanocarpa). Nutrients. 2020; 12(2): 463. https://doi.10.3390/ nu12020463.
Jurikova T, Mlcek J, Skrovankova S, et al. Fruits of Black Chokeberry Aronia melanocarpa in the Prevention of Chronic Diseases. Molecules. 2017; 22(6): 944. https://doi.10.3390/molecules2....
Szopa A, Kokotkiewicz A, Kubica P, et al. Comparative analysis of different groups of phenolic compounds in fruit and leaf extracts of Aronia sp.: A. melanocarpa, A. arbutifolia, and A. prunifolia and their antioxidant activities. Eur Food Res Technol. 2017; 243: 1645–1657.
Jurendić T, Ščetar M. Aronia melanocarpa Products and By-Products for Health and Nutrition: A Review. Antioxidants (Basel). 2021; 10(7): 1052. https://doi.10.3390/antiox1007....
Zielińska-Przyjemska M, Olejnik A, Grajek W. Wpływ soku z buraka ćwikłowego i aronii in vitro na metabolizm tlenowy i apoptozę ludzkich granulocytów obojętnochłonnych. Żywn Nauk Technol Jakość. 2007; 51(2): 174–186.
Li D, Wang P, Luo Y, et al. Health benefits of anthocyanins and molecular mechanisms: Update from recent decade. Crit Rev Food Sci Nutr. 2017; 57(8): 1729–1741. https://doi.10.1080/10408398.2....
Li L, Li J, Xu H, et al. The Protective Effect of Anthocyanins Extracted from Aronia Melanocarpa Berry in Renal Ischemia-Reperfusion Injury in Mice. Mediators Inflamm. 2021; 2021: 7372893. https:// doi.10.1155/2021/7372893.
Sikora J, Markowicz M, Mikiciuk-Olasik E. Rola i właściwości lecznicze aronii czarnoowocowej w profilaktyce chorób cywilizacyjnych. Bromat Chem Toksykol. 2009, 17(1): 10–17.
Jang BK, Lee JW, Choi H, et al. Aronia melanocarpa Fruit Bioactive Fraction Attenuates LPS-Induced Inflammatory Response in Human Bronchial Epithelial Cells. Antioxidants (Basel). 2020; 9(9): 816. https:// doi.10.3390/antiox9090816.
Chojnacka K, Witek-Krowiak A, Skrzypczak D, et al. Phytochemicals containing biologically active polyphenols as an effective agent against Covid-19-inducing coronavirus. J Funct Foods. 2020; 73: 104146. https:// doi.10.1016/j.jff.2020.104146.
Zhang DH, Wu KL, Zhang X, et al. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. J Integr Med. 2020; 18(2): 152–158. https://doi.10.1016/j.joim.202....
Todorova V, Ivanov K, Delattre C, et al. Plant Adaptogens-History and Future Perspectives. Nutrients. 2021; 13(8): 2861. https://doi.10.3390/ nu13082861.
Panossian AG, Efferth T, Shikov AN, et al. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases. Med Res Rev. 2021; 41(1): 630–703. https://doi.10.1002/med.21743.
Panossian A, Brendler T. The Role of Adaptogens in Prophylaxis and Treatment of Viral Respiratory Infections. Pharmaceuticals (Basel). 2020; 13(9): 236. https://doi.10.3390/ph13090236.
Panossian A, Seo EJ, Efferth T. Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology. Phytomedicine. 2018; 50: 257–284. https://doi.10.1016/j. phymed.2018.09.204.
Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017; 1401(1): 49–64. https://doi.10.1111/nyas.13399.
Domínguez R, Zhang L, Rocchetti G, et al. Elderberry (Sambucus nigra L.) as potential source of antioxidants. Characterization, optimization of extraction parameters and bioactive properties. Food Chem. 2020; 330: 127266. https://doi.10.1016/j.foodchem....
Porter RS, Bode RF. A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products. Phytother Res. 2017; 31(4): 533–554. https://doi.10.1002/ptr.5782.
Waknine-Grinberg JH, El-On J, Barak V, et al. The immunomodulatory effect of Sambucol on leishmanial and malarial infections. Planta Med. 2009; 75(6): 581–6. https://doi.10.1055/s-0029-118....
Wen K, Fang X, Yang J, et al. Recent Research on Flavonoids and their Biomedical Applications. Curr Med Chem. 2021; 28(5): 1042–1066. https://doi. 10.2174/0929867327666200713184138.
Saluk-Juszczak J. Antocyjany jako składnik żywności funkcjonalnej stosowanej w profilaktyce chorób układu krążenia. Post Hig Med Dośw. 2010; 64: 451–458.
Mousa HA. Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies. J Evid Based Complementary Altern Med. 2017; 22(1): 166– 174. https://doi.10.1177/2156587216....
Brendler T, Al-Harrasi A, Bauer R, et al. Botanical drugs and supplements affecting the immune response in the time of COVID-19: Implications for research and clinical practice. Phytother Res. 2021; 35(6): 3013–3031. https://doi.10.1002/ptr.7008.
Salman H, Bergman M, Bessler H, et al. Effect of a garlic derivative (alliin) on peripheral blood cell immune responses. Int J Immunopharmacol. 1999; 21(9): 589–97. https://doi.10.1016/s0192-0561....
Marciniec K, Włodarczyk-Marciniec B. Przeciwnowotworowe właściwości czosnku. Post Fitoter. 2008; 2: 90–95.
Arreola R, Quintero-Fabián S, López-Roa RI, et al. Immunomodulation and anti-inflammatory effects of garlic compounds. J Immunol Res. 2015; 15:401630. https://doi.10.1155/2015/40163....
Lv Y, So KF, Wong NK, et al. Anti-cancer activities of S-allylmercaptocysteine from aged garlic. Chin J Nat Med. 2019; 17(1):.43–49. https://doi.10.1016/S1875-5364....
Choo S, Chin VK, Wong EH, et al. Review: antimicrobial properties of allicin used alone or in combination with other medications. Folia Microbiol (Praha). 2020; 65(3): 451–465. https://doi.10.1007/s12223- 020-00786-5.
Ali BH, Blunden G, Tanira MO, et al. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol. 2008; 46(2): 409–20. https://doi.10.1016/j.fct.2007....
Zhou HL, Deng YM, Xie QM. The modulatory effects of the volatile oil of ginger on the cellular immune response in vitro and in vivo in mice. J Ethnopharmacol. 2006; 105(1–2): 301–5. https://doi.10.1016/j. jep.2005.10.022.
Fouda AM, Berika MY. Evaluation of the effect of hydroalcoholic extract of Zingiber officinale rhizomes in rat collagen-induced arthritis. Basic Clin Pharmacol Toxicol. 2009; 104(3): 262–71. https://doi.10.1111/j.1742- 7843.2008.00363.x.
Bałan B, Różewski F, Zdanowski R, et al. Immunotropic activiy of Echinacea. Part I. History and chemical structure. Central. European Journal of Immunology. 2012; 37(1): 45–50. https://doi. org/10.1177/1934578X1400900422.
Aucoin M, Cooley K, Saunders PR, et al. The effect of Echinacea spp. on the prevention or treatment of COVID-19 and other respiratory tract infections in humans: A rapid review. Adv Integr Med. 2020; 7(4): 203–217. https://doi.10.1016/j.aimed.20....
Bałan B, Różewski F, Skopińska-Różewska E, et al. Immunotropic activiy of Echinacea. Part II. Experimental and clinical data. Central European Journal of Immunology. 2012; 37(1): 51–56.
Schoop R, Klein P, Suter A, et al. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis. Clin Ther. 2006; 28(2): 174–183. https://doi.10.1016/j.clinther....
Shah SA, Sander S, White CM, et al. Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis. Lancet Infect Dis. 2017; 7(7): 473–480. https://doi.10.1016/S1473-3099....
Schapowal A, Klein P, Johnston SL. Echinacea reduces the risk of recurrent respiratory tract infections and complications: a meta-analysis of randomized controlled trials. Adv Ther. 2015; 32(3): 187–200. https:// doi.10.1007/s12325-015-0194-4.
Liu W, Zhai Y, Heng X, et al. Oral bioavailability of curcumin: problems and advancements. J Drug Target. 2016; 24(8): 694–702. https://doi.10.3109/1061186X.2....
Pagano E, Romano B, Izzo AA, et al. The clinical efficacy of curcumincontaining nutraceuticals: An overview of systematic reviews. Pharmacol Res. 2018; 134: 79–91. https://doi.10.1016/j.phrs.201....
Zahedipour F, Hosseini SA, Sathyapalan T, et al. Potential effects of curcumin in the treatment of COVID-19 infection. Phytother Res. 2020; 34(11): 2911–2920. https://doi.10.1002/ptr.6738.
Shanmugarajan D, Prabitha P, Kumar B.P, et al. Curcumin to inhibit binding of spike glycoprotein to ACE2 receptors: Computational modelling, simulations, and ADMET studies to explore curcuminoids against novel SARS-CoV-2 targets. RSC Advances. 2020; 10(52): 31385–31399.
Pagano E, Romano B, Izzo AA, et al. The clinical efficacy of curcumin-containing nutraceuticals: An overview of systematic reviews. Pharmacol Res. 2018; 134: 79–91. https://doi.10.1016/j.phrs.201....
Sordillo PP, Helson L. Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections. In Vivo. 2015; 29(1): 1–4.
Zhang CX, Wang HY, Chen TX. Interactions between Intestinal Microflora/Probiotics and the Immune System. BioMed research international. 2019; 676: 4919.
Anand S, Mande SS. Diet, Microbiota and Gut-Lung Connection. Frontiers in microbiology. 2018; 9: 2146.
Mosca A, Leclerc M, Hugot JP. Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem? Frontiers in microbiology. 2016; 7: 455.
Rishi P, Thakur K, Vij S, et al. Diet, Gut Microbiota and COVID-19. Indian journal of microbiology. 2020; 60(4): 420–429.
Aktas B, Aslim B. Gut-lung axis and dysbiosis in COVID-19. Turkish journal of biology = Turk biyoloji dergisi. 2020; 44(3): 265–272.
Budden KF, Gellatly SL, Wood DL, et al. Emerging pathogenic links between microbiota and the gut-lung axis. Nature reviews. Microbiology. 2017; 15(1): 55–63.
Dumas A, Bernard L, Poquet Y, et al. The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases. Cellular microbiology. 2018; 20(12): 12966.
Iddir M, Brito A, Dingeo G, et al. Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis. Nutrients. 2020; 12(6): 1562.
Farsi Y, Tahvildari A, Arbabi M, et al. Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review. Frontiers in cellular and infection microbiology. 2022; 12: 804644.
De Filippis F, Pellegrini N, Vannini L, et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2016; 65(11): 1812–1821.
Meyer D, Stasse-Wolthuis M. The bifidogenic effect of inulin and oligofructose and its consequences for gut health. Eur J Clin Nutr. 2009; 69: 1277–1289.
Bouhnik Y, Achour L, Paineau D, et al. Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal bifidobacteria and cholesterol excretion in healthy elderly volunteers. Nutrition Journal. 2007; 6: 42.
Keim NL, Martin RJ. Dietary Whole Grain–Microbiota Interactions: Insights into Mechanisms for Human Health. Advances in Nutrition. 2014; 5(5); 556–557.
Trompette A, Gollwitzer E, Yadava K, et al. Gut microbiota metabolism of dietary fibre influences allergic airway disease and hematopoiesis. Nat Med. 2014; 20: 159–166.
Watanabe Y, Allen JD, Wrapp D, et al. Site-specific glycan analysis of the SARS-CoV-2 spike. Science New York. 2020; 369(6501): 330–333.
Mörbe UM, Jørgensen PB, Fenton TM, et al. Human gut-associated lymphoid tissues (GALT); diversity, structure, and function. Mucosal immunology. 2021; 14(4): 793–802.
Ishizuka S, Tanaka S. Modulation of CD8+ Intraepithelial Lymphocyte Distribution by Dietary Fibre in the Rat Large Intestine. Experimental Biology and Medicine. 2002; 227(11): 1017–1021. https://doi.10.1177/1535370202....