MANAGEMENT AGAINST COVID-19 THROUGH NUTRITIONAL SUPPLEMENTATION TO BUILD ADAPTIVE IMMUNITY – A SYSTEMATIC REVIEW

MANAGEMENT AGAINST COVID-19 THROUGH NUTRITIONAL SUPPLEMENTATION TO BUILD ADAPTIVE IMMUNITY - A SYSTEMATIC REVIEW

Luxita Sharma

Dietetics and Applied Nutrition, Gurugram - 122002, Haryana, India.

ABSTRACT: As humanity is progressing, many new borne infections are borne, and the stability and efficiency of the human body are being tested. Today the World is fighting with a deadly Novel infection named Corona Virus Disease. The aim of this systematic review is to find out the efficacy of Nutritional Interventions against the infections caused in the body due to pathogens. Further, the recommendations can be made for further researches based on the evidence collected. To collect the data, electronic databases such as Scopus, Pub Med, NCBI, and web of science have been used. The peer-reviewed journals and newspaper reports are being cited with the English language. The papers were published from 1989 to 2020. Finally, a total of twelve studies were identified, and the pathways of all nutrient metabolisms are included in the study. The studies were mostly carried out in Asian and European countries on human as well as animals. All the studies except one supported the role of Nutrients in preventing and curing the infection caused by pathogens such as Bacteria and Viruses. The Dietary Interventions in any form were proven to have a positive effect on strengthening the Immune system and also curing the disease. The results are supporting that Adaptive immunity can help a person to fight with COVID-19. Mostly the adaptive immunity is built by vaccinations or certain medications. But many researches showed that a diet filled with nutrients and the right choices of food can help to build adaptive immunity.

COVID-19, Adaptive Immunity, Nutrition, Vitamins, Minerals, Immune system

INTRODUCTION: Coronavirus disease (COVID-19) is an infectious disease caused by a novel coronavirus called SARS-CoV-2 ¹. The symptoms of COVID-19 are respiratory problems and breathing difficulty. The patient experiences flu like symptoms. The sequence analysis showed that the COVID‐19 has a distinct genome structure that belonged to the cluster of β‐coronaviruses, including SARS‐CoV and MERS‐CoV^2.One can protect self by washing hands frequently, avoiding touching face and avoiding close contact (maintaining 1 meter or 3 feet) with people who are infected ^{1, 2, 3}.

Immunity is basically acquired by the body in two ways; one is the innate immunity, while the other one is adaptive immunity. Innate immunity or the native immunity has its existence from the genes and is not induced artificially through drugs or other external stimulation. It is of two types as (a) Non-Specific innate immunity, which provides resistance to all general infections. Specific innate immunity is the inborn resistance to a particular kind of microorganism. Adaptive immunity is what is acquired through time and contact with a disease-causing agent, by an introduction to deliberate actions such as vaccination ³. Research Objective To find a Nutritional Cure or Management for COVID-19 through Nutritional supplementation.

MATERIALS AND METHODS:

Role of Nutrients and to strengthen the Adaptive Immunity: The main aim of this review is to impart knowledge to the community about the importance of immune system to fight the diseases. The present scenario all over the world is to fight with COVID-19 and make different strategies to kill this virus. This review paper is an attempt to help people to manage this disease with their dietary intake. The major limitation is that immunity takes a longer duration of time to be built and we have very less time. But we can try to improve our immune system so that we can efficiently fight with this virus borne disease. But we have to remember that Nutrition supplementation is to be provided to fight the COVID-19.

Tools for Collecting Literature Review: To collect the data electronic databases such as Scopus, Pub Med, NCBI and web of science have been used. The papers were published from 1989 to 2020. Finally, a total of eleven studies were identified and the pathways of all nutrient metabolisms are included in the study. The studies were mostly carried out in Asian and European countries on human as well as animals. The References were checked manually from the reviews and systemic reviews so that they were not identified during the whole search process.

Inclusion and Exclusion Criteria: The studies which correlated the food intake with the building of immunity through nutrients were taken and included.

The studies were also focussed on improving the adaptive immunity by fortification of the nutrients. The studies having gene expressions or drug studies were excluded. Medicinal or herbal studies were also excluded.

Data Extraction: A single-minded approach was used to find out the research being carried out on the role of nutrients to increase immunity.

The country, study design, description of the pathways that how immunity is built was included and then the main results were jotted down.

Data Analysis: A narrative synthesis was taken because no uniformity in the case studies was found in terms of the population, gender, or ethnicity. And Metanalysis was not possible in this paper.

RESULTS:

Nutrients: Their pathways and Case Studies in Strengthening Immune System.

Vitamin A:

Nutritional Recommendations to Increase Immunity: Nutrition acts as a modifiable factor in impacting immune system function, and researches in this field are called as Nutritional Immunology. Below are some of the major nutrients that qualify to maintain our Adaptive immunity ⁴¹.

Twelve Studies were finally included in the paper. Studies not supporting or with no results shown were excluded. One case study is from recent newspaper reading and rests eleven are from the review papers

FIG. 1: PRISMA DIAGRAM SHOWING THE SCREENING PROCESS

FIG. 2: STRUCTURE VITAMIN A ⁴¹

Vitamin A is a type of fat-soluble vitamin. It is a group of unsaturated monohydric alcohols containing an alicyclic ring ⁴. Vitamin A is the most popular nutrient which is studied and recommended to improve immunity. An obser-vation was made that there is a strong link between vitamin A and immunity, even before the structure of vitamin A was deduced ⁵. Vitamin A is called as the “anti-inflammation vitamin”. It has ability to boost the body’s system against the possible attack of pathogens and activate the anti-inflammatory response of the body. Both the innate and adaptive immunity system is affected by the role of vitamin A as it promotes and regulates immune system; thus, enhancing the functions of the immune system and increases the capability of the body to fight against a number of infectious diseases ⁶ Vitamin A can be obtained from the diet in the form of all-trans-retinol, retinyl esters or β-carotene.

The food products rich in Vitamin A are all yellow food products such as Pumpkin, Carrots, Broccoli, Spinach, Squash, Sweet potato, Mangoes, Papaya, Cantaloupes, Apricots, and fortified Breakfast cereals. Antibody production by B cells is central to humoral homeostatic maintenance. Antibodies represent a specific class of immunoglobulins ^{36, 37}.

Animal experiments have demonstrated that the addition of carotenoid-rich foods to rabbit diets can increase their serum levels of IgG, IgM and IgA, thereby enhancing humoral immunity ⁷ Vitamin A metabolites affect the adaptive immunity in human body in the most positive way. The Retinoic acid enhances the B and T cell activation, which are responsible for increasing immunity in Human Body. The pathways go as suppose an inflammatory factor is present in body, then the stored Retinoic Acid enhances DC maturation with further increment of IL-2, which activates the B and T cells and the adaptive response is activated ⁸.

FIG. 3: PATHWAY OF THE ACTION OF VITAMIN A AND ADAPTIVE IMMUNITY

Vitamin C:

FIG. 4: STRUCTURE OF VITAMIN C⁴¹

Vitamin C or ascorbic acid is a water-soluble vitamin. The immune system of the body is supported by vitamin C.  Vitamin C supplementation has been able to both prevent and treat respiratory and systemic infections and improves activities of the immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis and delayed-type hypersensitivity ^9. Vitamin C helps to strengthen the immune system in the following ways: 1). by enhancing the synthesis and stabilization of collagen, 2). providing protection against damages induced by ROS, 3). aiding the process of wound healing, 4). acting as an antioxidant, 5). enhancing phagocytosis & microbial killing and decreasing necrosis, 6). enhancement of levels of antibodies & 7). Through modulating cytokines production etc. ^{9, 10, 11}. The food products rich in Vitamin C are Amla, Lemon, Guava, Oranges, Fruit juices, and tomatoes. According to a Newspaper report, Vitamin C supplementation in high doses of about 1500 mg intravenously was effective for the recovery of Patients suffering from COVID-19. This line of treatment is being used in New York as well as China ¹². The immune mediator Histamine is given birth by Eosinophils, Basophils and mast cells. The Histamines are produced at greater levels when the body is in stress and results in the increased symptoms of allergy like flu and others. Histamine increases in body, and Vitamin C is depleted in the body. A study was carried on guinea pigs, they were provided with Vitamin C supplementation, and it showed a decrease in Histamine levels, thus reducing the allergy symptoms ^{13, 14}. The intervention of oral Vitamin C 125 mg per day has helped to decrease histamine levels in patients having allergy symptoms ¹⁵.

FIG. 5: FUNCTIONS OF VITAMIN C IN HUMAN BODY

Vitamin C has a role in phagocytosis; it increases Neutrophil migration whenever there is chemotaxis and enhances the engulfment of microbes. The Oxidative species of reactive oxygen is increased and it results in killing of microorganisms ^{13, 39}. The animals who were deficient of Vitamin C showed the microbial invasion, and infection resulted. The generation of reactive oxygen species with the help of neutrophils is enhanced by the supplementation of Vitamin C by 20 percent. A study showed that patients with recurrent infections had impaired Microbial deaths in the body so, with the supplementation of Vitamin C through diet or intravenously, resulted in the killing of infection and condition of the patients improved significantly ^{40, 41}. This supports the improvement in the condition of COVID-19 patients with Vitamin C supplementation ¹⁶.

Vitamin E: Vitamin E is a fat-soluble antioxidant vitamin. It is also one of the most important vitamins needed for the proper functioning of the immune system. Even a minor deficiency of this vitamin can affect the efficiency of the immune response ⁴¹. Supplementation of vitamin E has shown to have various advantages on the immune system, such as increased levels of immune-globulin, lymphocyte proliferation, anti-body responses, natural killer (NK) cell activity and interleukin (IL)-2 productions, enhanced resistance to some specific pathogens and infections ¹⁷. All the vegetable oils and Nuts and oilseeds contain Vitamin E ⁴¹. A case study carried out has shown that Vitamin E supplementation has enhanced immunity in old aged people. The Healthy elderly population was administered with 800 mg 2-ambo-α-tocopherol or placebo/d for 30 days. The results showed increased DTH levels, which is an indicator of cell-mediated immunity. Further, it was found that Vitamin E is related to increased plasma Vitamin E, DTH score, Mitogenic response. These all factors are related to the immunity build up in the body ¹⁷. Vitamin E supplementation of1500 IU d-α-tocopheryl acetate/day for 16 weeks in allergic asthmatic patients resulted in the oppression of alveolar macrophage nuclear factor (erythroid-derived 2)-like 2 (NRF2) activity. This study has positively correlated the role of Vitamin E in managing and preventing the respiratory disorders Fig. 6 ¹⁸

FIG. 6: STRUCTURE OF VITAMIN E ⁴¹

FIG. 7: ROLE OF VITAMIN E IN INFECTIOUS DISEASES IN HUMANS

Vitamin B₉: Also known as folate, it is an essential vitamin for the synthesis of DNA and protein in the body. It is an essential vitamin as it is not synthesized by the body and hence needs to be supplemented through food and drugs. Deficiency of folate affects the immune system adversely since it limits the activities of growth and cell division and also interferes with the production of red blood cells (erythropoiesis) ^{19, 20}. The vitamin B9 rich foods are green leafy vegetables and nuts ⁴¹. Vitamin B9 is required for the survival of Foxp3⁺ Treg cells. Studies have shown that Vitamin B9 is responsible for increased levels of Foxp ^3-20. Dietary vitamin B9 maintains Foxp3⁺ Treg cells in the small intestine, A study was carried out in mice, and it showed that Mice maintained with vitamin B9(-) diet showed less vitamin B9 in the small-intestinal wash than controls. In contrast, the amounts of vitamin B9 in the large-intestinal wash and serum were not different in those mice presumably due to vitamin B9 production from commensal bacteria ¹⁹. Vitamin B9 or Folate is mandatory for the production of protein synthesis. So, Folate deficiency can result in a compromised immune system. The activity of CD8⁺ T cells and NK cells can be declined due to folate insufficiency, and this declination can result in low resistance of the body to infectious diseases ²¹.

FIG. 8: STRUCTURE OF VITAMIN B9 ⁴¹

Zinc: Zinc is a very important micronutrient needed by the human body when it comes to the immunity. It helps in normal functioning and development of the human cells, which arbitrate the working of innate immunity, killer cells, macro-phages and neutrophils ⁴¹.

Zinc not only aids the function of the immune system by supporting it to act as a barrier to infection but also affects the gene regulation within lymphocytes. The deficiency of zinc increases the chances of infection and makes the person more prone to a variety of pathogens.

Activities of the human body such as phagocytosis, intracellular killing, and cytokine production are also affected in the state of zinc deficiency ²². The food products rich in Zinc are Red Meat and Oysters.

The fair sources are grains, peanuts, fruits, and green leafy vegetables. Zinc has a mechanism of getting absorbed through intestines by specific zinc transporting and bound proteins such as albumin, α₂-macroglobulin (A2M), and transferring ²³.

Studies show that Patients suffering from Viral Infections such as HIV, Common cold, Chronic Diarrhea or Chronic Hepatitis OR some bacterial infections such as Helicobacter pylori or any disease of autoimmune disorders benefit from Zinc Supplementation.

Though Zinc deficiency is hard to diagnose but it is a major nutrient that regulates our immunity. Zinc Homeostasis is essential for haematopoiesis, cell differentiation, and maturation, etc. Whenever our body has inflammatory disorders adequate zinc supplementation improves condition ²⁴.

FIG. 9: PATHWAY OF ZINC IN BUILDING ADAPTIVE IMMUNITY

Copper: Copper is also an essential trace micronutrient for the human body for survival. It is a necessity for proper growth, metabolism of iron, functioning of neuroendocrine, elasticity of lungs, cardiovascular integrity and neovascularisation. Deficiency of copper leads to decreased levels of IL-2, T cell proliferation and also reduces the ability to generate superoxide anion and kill ingested microorganisms ²⁵. The food products which are good sources of copper are oysters, nuts, seeds, shitake mushrooms, lobster, liver, leafy greens , and dark chocolate ⁴¹.

Iron: Iron is a much-needed nutrient for normal functioning of immune and non-immune cells biochemical reactions. The effect of the iron homeostasis on the immune function and risk of infection has been recognized in the 1970s ²⁶ Iron is an important nutrient for proliferation and maturation of immune cells, especially lympho-cytes. Not only the deficiency but also the excess of iron can affect the normal functioning of the innate and adaptive parts of the immune system. Excess of iron assists in the development of infections and invasion of diseases ²⁷. The foods rich in Iron are red meats, nuts, garden cress seeds, fruits rich in vitamin C will enhace iron absorption and liver of chicken and lamb ⁴¹.

Iron and Adaptive Immunity: Antigen-specific B and T lymphocytes proliferation starts as the body is being attacked by any foreign material. So, a number of studies were carried out and was found that Iron deficiency can result in impaired phyto-hemagglutin in induced lymphocyte proliferation and delayed-type hypersensitivity responses with relative preservation of humoral immunity ²⁸. Therefore it is being correlated that Iron is important for lymphocyte working in the body in times of infection ⁴¹.

FIG. 10: ROLE OF IRON REGULATORY HORMONE HEPCIDIN IN RESPONSE TO INFECTIONS ²⁶

The anti-pathogen response of Human body is related to the status of Iron in the system. The infections such as Malaria and Tuberculosis are treated with supplementation of Iron and the success rate is also excellent. The status of the Iron in the body is associated with chronic infections. The link between the non-functional immunity and Iron homeostasis has shown that the transcription factor HIF-1α, which has well-known functions in the immune response, Iron-dependent modulation of NF-κB activation and TLR4 signalling. Iron is being linked positively with combating the infections in the body ²⁹.

Selenium: Selenium, in combination with seleno-proteins, plays a very crucial role in the maintenance of human health. The deficiency of selenium has been associated with increased susceptibility to diseases caused due to oxidative stress, while supplementation of selenium showed increased resistance to diseases and viral infections ³⁰. Selenium influenced both the components of the immune system- innate, the non-adaptive one, and acquired the adaptive one. It can also be called as an immunity booster; selenoproteins play a very important part in oxidative stress reduction and redox balancing in tissues and cell types ³². The food products rich in selenium are Pork, beef, turkey, chicken, fish, shellfish, and eggs ⁴¹.

Selenium and Viral Infections: The studies conducted at Beck Laboratory on mice showed that Selenium deficiency alters the immune system under the attack of viral infections.

It was studied that the mice suffering from influenza were having inflammation due to higher levels of oxidative stress. It was found in early stages of the infection that macrophages were present at larger levels with selenium deficiency, and later, the levels of macrophages, CD8⁺ , and CD4⁺ T cells were lower in Se-deficient mice. This showed that Se-deficiency affects cell-mediated immunity to a greater extent than humoral immunity for anti-influenza viral responses in this model ^{30, 31}. Selenium is said to increase the general immunity but the mechanism or the pathway that selenium takes to increase immunity is still not very clear ³².

TABLE 1: RECOMMENDED DIETARY ALLOWANCES FOR INDIANS TO INCREASE IMMUNITY

Source – ICMR, 1989, 2007 40, mg - milli grams

CONCLUSION: Nutrition and Infection works as a good nutritional status leads to less infections and vice versa. The deficiency prevailing in body could be improved by supplementation of Nutrients in accordance to recommended dietary allowances, which could strengthen the immune system in return. Adaptive Immunity is the system that our body designs to fight any foreign body, which is new to the human system. So this theory itself explains the people recovering from corona attack are young people with strong immunity, Old age people have weakened immunity and same is with the children. According to World Health Organization (WHO) 55 years is the beginning of old age and also WHO says that the old age is the start of losing active life, loss of previous roles, or inability to make active contributions to society. The ageing results from the destruction of cells at molecular levels and then there is slow reduction in the physical and mental capability and then old people become prone to diseases and untimely death ⁵. One of the most important factors adding up to the competency of the immune system is the nutritional status.

If a person is undernourished, he/she is more susceptible to infection and diseases since the activities of the immune system get suppressed due to lack of energy and important nutrients intake. The other reason can be specific nutrient or of more than one nutrient deficiency Essential nutrients needed for the efficient functioning of the immune system include Vitamin A, Vitamin C, Vitamin E, Essential amino acids, Essential fatty acid, Linoleic acid, Folic acid, Zinc, Copper, Iron and Selenium ³⁹. The infections prevail according to life cycle like the infants and geriatrics population has weak immunity. And it can be altered with interventions easily. The intervention features can be a vaccine or drugs or the dietary intake with lifestyle changes. The dietary supplementation should be tailormade in accordance to the age, gender, ethnicity and heredity as well ^{33, 34}.

The present review encapsulates that micronutrients in diet or in form of fortification can result in recovery from the disease. The deficiency of micronutrients may lead to the development of many infections due to pathogens and also decrease the body’s ability to fight with life threatening infection such as COVID -19. We are not claiming the treatment of the COVID-19, but the life-threatening diseases could be managed well through the sufficient supply of micro and macronutrients; therefore a balanced diet can increase the chances to fight back with the infections.

ACKNOWLEDGEMENT: Nil

CONFLICTS OF INTEREST: Nil

REFERENCES:

1. "Naming the coronavirus disease (COVID-19) and the virus that causes it". World Health Organization (WHO). Archived from the original on 28 February 2020. Retrieved 28 February 2020.
2. Li-sheng Wang, Yi-ru Wang, Da-wei Ye and Qing-quan Liu: A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence, International Journal of Antimicrobial Agents 2020; 10(1016): 105948.
3. Moulin and Anne-Marie: The immune system: a key concept for the history of immunology. History and Philosophy of the Life Sciences 1989; 11(2): 221-36.
4. Calder PC and Kew S: The immune system: a target for functional foods. The Briti J of Nut 2002; 88 (2): 165-77.
5. Luxita Sharma: Correlation among the nutritional, mental and physiological factors affecting the health and lifestyle of geriatrics population. International Journal of Scientific & Technology Research 2019; 8(10): 2936-48.
6. Iddir M, Brito A and Dingeo G: 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.
7. Huang Z, Liu Y, Qi G, Brand D and Zheng SG: Role of Vitamin A in the Immune System. Journal of Clinical Medicine 2018; 7(9): 258.
8. Calder PC: Nutrition, immunity and COVID-19. BMJ Nutrition, Prevention & Health 2020; bmjnph-2020-000085. Doi: 10.1136/bmjnph-2020-000085.
9. Mousavi S, Bereswill S and Heimesaat MM: Immuno-modulatory and Antimicrobial Effects of Vitamin C. Eur J Microbiol Immunol Bp 2019; 9(3): 73-79.
10. Nandi BK, Subramanian N, Majumder AK and Chatterjee IB: Effect of ascorbic acid on detoxification of histamine under stress conditions. Biochem Pharmacol 1974; 23: 643-47.
11. Hemilä H and Chalker E: Vitamin C as a Possible Therapy for COVID-19. Infect Chemother 2020; 52(2): 222-23. doi:10.3947/ic.2020.52.2.222
12. New York hospitals are treating coronavirus patients with high dosages of VITAMIN C after promising results from China Vitamin By Matthew Wright For Dailymail.Com ;Published: 00:20 bst, 25 march 2020 | updated: 14:46 bst, 25 march 2020.
13. Q & A on coronaviruses (COVID-19)". World Health Organization (WHO). Archived from the original on 20 January 2020. Retrieved 11 March 2020.
14. Iddir M, Brito A and Dingeo G: 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.
15. "Symptoms of Coronavirus". U.S. Centers for Disease Control and Prevention (CDC). 10 February 2020. Archived from the original on 30 January 2020.
16. Wong SK, Chin KY and Ima-Nirwana S: Vitamin C: A Review on its Role in the Management of Metabolic Syndrome. Int J Med Sci 2020; 17(11): 1625-38. Published 2020 Jun 27. doi:10.7150/ijms.47103
17. Nicholson LB: The immune system. Essays in Biochemistry 2016; 60(3): 275-01.
18. Lee-Gaa, Young and Han-Sung Nim: The Role of Vitamin E in Immunity. Nutrients 2018; 10(11): 1614.
19. Mikkelsen K and Apostolopoulos V: Vitamin B12, folic acid, and the immune system. in: mahmoudi m., rezaei n. (eds) nutrition and immunity. Springer Cham 2019; 103-14; https://doi.org/10.1007/978-3-030-16073-9_6.
20. Yamaguchi T, Hirota K and Nagahama K: Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 2007; 27(1): 145-159. doi:10.1016/j.immuni.2007.04.017.
21. Yoshii K, Hosomi K, Sawane K and Kunisawa J: Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity. Front Nutr 2019; 6: 48. Published 2019 Apr 17. doi:10.3389/fnut.2019.00048
22. Wessels I, Rolles B and Rink L: The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis. Front Immunol 2020; 11: 1712. Published 2020 Jul 10. doi:10.3389/fimmu.2020.01712
23. Wessels I, Maywald M and Rink L: Zinc as a gatekeeper of immune function. Nutrients 2017; 9: 1286.
24. Shankar AH and Prasad AS: Zinc and immune function: the biological basis of altered resistance to infection. The American J of Clinical Nutrition 1998; 68(2): 447-63.
25. Percival SS: Copper and immunity. The American Journal of Clinical Nutrition 1998; 67(5): 1064-68.
26. Rossi Ep: Hepcidin the iron regulatory hormone. Clin Biochem Rev 2005; 26(3): 47-49.
27. Cherayil BJ: Iron and immunity: immunological consequences of iron deficiency and overload. Arch. Immunol Ther Exp 2010; 58: 407-15.
28. Kuvibidila SR, Baliga SB, Chandra LC and French CL: The role of iron in immunity and inflammation: implications for the response to infection. Diet Immunity and Inflammation 2013; 1: 193-20.
29. Soyano A and Gomez M: Role of iron in immunity and its relation with infections. Arch Latinoam Nutrition 1999; 49(3): 40-46.
30. Moghaddam A, Heller RA and Sun Q: Selenium Deficiency Is Associated with Mortality Risk from COVID-19. Nutrients 2020; 12(7): 2098. Published 2020 Jul 16. doi:10.3390/nu12072098.
31. Hoffmann PR and Berry MJ: The influence of selenium on immune responses. MNFR 2008; 2(11): 1273-80.
32. Maggini S, Pierre A and Calder PC: Immune function and micronutrient requirements change over the life course. Nutrients 2018; 10: 1531.
33. Timoneda J, Rodríguez-Fernández L and Zaragozá R: Vitamin a deficiency and the lung. Nutrients. 2018; 10(9): 1132. Published 2018 Aug 21. doi:10.3390/nu10091132.
34. Zhang J, Taylor EW, Bennett K, Saad R and Rayman MP: Association between regional selenium status and reported outcome of COVID-19 cases in China. American Journal of Clinical Nutrition. 2020; 111(6): 1297-99.
35. El-Zayat SR, Sibaii H, Mahfouz NN, Sallam SF, Fahmy RF and Abd El-Shaheed A: Effect of vitamin A deficiency on thymosin-β4 and CD4 concentrations. J of Genetic Engineering and Biotechnology 2018; 16(1): 57-61.
36. Ghodratizadeh S, Kanbak G, Beyramzadeh M, Dikmen ZG, Memarzadeh S and Habibian R: Effect of carotenoid β-cryptoxanthin on cellular and humoral immune response in rabbit. Vet Res Commun 2014; 38: 59-62.
37. Carr AC and Maggini S: Vitamin C and Immune Function. Nutrients 2017; 9(11): 1211.
38. Rowe S and Carr AC: Global Vitamin C status and prevalence of deficiency: a cause for concern. Nutrients 2020; 12(7): 2008.
39. Gombart AF, Pierre A and Maggini S: A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients 2020; 12(1): 236.
40. Gopalan C, Rama Sastri BV and Balasubramanian S: “Nutritive Value of Indian Foods” published by National Institute of Nutrition (NIN) ICMR 2007.
41. Sharma L: Dietary management to build adaptive immu-nity against COVID19. J of Peer Sci 2020: 2(2): 2581-21.
    

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    How to cite this article:

    Sharma L: Management against Covid-19 through nutritional supplementation to build adaptive immunity - a systematic review. Int J Pharm Sci & Res 2020; 11(9): 4114-22. doi: 10.13040/IJPSR.0975-8232.11(9).4114-22.

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