Selected Micronutrients: An Option to Boost Immunity against COVID-19 and Prevent Adverse Pregnancy Outcomes in Pregnant Women: A Narrative Review
The coronavirus disease-19 (COVID-19) negatively affects immune system. It is linked with adverse pregnancy outcomes. These complications may be linked with the infections mediated deficiency of micronutrients in pregnant women. COVID-19 cause’s malabsorption of micronutrients thereby increases the risk of their deficiency. Both micronutrients deficiencies and poor micronutrients intake can compromise immune function and may increase the risk of pregnancy complications associated with COVID-19 infection. Vitamin A, C, D, E, and selected minerals iron (Fe), selenium (Se), and zinc (Zn) are the micronutrients essential for immuno-competency and play a significant role in the prevention of adverse pregnancy outcomes. Immune function and pregnancy outcomes can be improved by adequate intake of micronutrients in diet or in supplements form. Based on regulatory links between viral infection, micronutrients, immunity, and pregnancy outcomes, this review highlights the role of micronutrients in boosting immunity to reduce or prevent pregnancy complications in COVID-19 infected women.
2. World Health Organization. WHO Di-rector-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020
3. Covid-19 coronavirus pandemic (2020). https://www.worldometers.info/coronavirus/. Last updated: October 01, 2020, 04:04 GMT.
4. Rasmussen SA, Jamieson DJ, Uyeki TM (2012). Effects of influenza on pregnant women and infants. Am J Obstet Gynecol, 207:S3–8.
5. CDC (2020). Coronavirus (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/
6. Zhu H, Wang L, Fang C, et al (2020). Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneu-monia. Transl Pediatr, 9(1): 51–60.
7. Wong SF, Chow KM, Leung TN, et al (2004). Pregnancy and perinatal out-comes of women with severe acute respiratory syndrome. Am J Obstet Gynecol, 191:292–7.
8. Alfaraj SH, Al-Tawﬁq JA, Memish ZA (2019). Middle East respiratory syn-drome coronavirus (MERS-CoV) infection during pregnancy: report of two cases & review of the litera-ture. J Microbiol Immunol Infect, 52(3):501–503.
9. Alpert P (2017). The role of vitamins and minerals on the immune sys-tem.
Home Health Care Management & Prac-tice, 29:199–202.
10. Calder P (2013). Conference on ‘Trans-forming the nutrition landscape in Africa’. Plenary Session 1: Feeding the immune system. Proc Nutr Soc, 72:299–309.
11. Rebecca LW, Jason AG, Dale M, et al (2018). Vitamin and mineral sup-plementation in pregnancy: evidence to practice. J Pharm Pract Res, 48:186–192.
12. Aghaeepour N, Ganio EA, Mcilwain D, et al (2017). An immune clock of human pregnancy. Sci Immunol, 2(15):eaan2946.
13. Giugliano S, Petroff MG, Warren BD, et al (2015). Hepatitis C virus sensing by human trophoblasts induces in-nate immune responses and re-cruitment of maternal NK cells: po-tential implications for limiting verti-cal transmission. J Immunol, 195: 3737-47.
14. Tian M, Zhang Y, Liu Z, et al (2016). The PD-1/PD-L1 inhibitory path-way is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats. Sci Rep, 6:27683.
15. Olivadoti M, Toth LA, Weinberg J, et al (2007). Murine gammaherpesvirus 68: a model for the study of Ep-stein-Barr virus infections and relat-ed diseases. Comp Med, 57(1):44-50.
16. García-Sastre A, Biron CA (2006). Type 1 interferons and the virus-host rela-tionship: a lesson in detente. Science, 312(5775):879-82.
17. Cappelletti M, Presicce P, Lawson MJ, et al (2107). Type I interferons regu-late susceptibility to inflammation-induced preterm birth. JCI Insight, 2(5):e91288.
18. Huang C, Wang Y, Li X, et al (2020). Clinical features of patients infected with 2019 novel coronavirus in Wu-han, China. The lancet, 395:497-506.
19. Mor G, Aldo P, Alvero AB (2017). The unique immunological and microbial aspects of pregnancy. Nature Reviews Immunology, 17:469-482.
20. Tetro JA (2020). Is COVID-19 receiv-ing ADE from other coronaviruses? Microbes and Infection, 22:72-73.
21. Shi L, Tu N, Patterson PH (2005). Ma-ternal inﬂuenza infection is likely to alter fetal brain development indi-rectly: the virus is not detected in the fetus. International Journal of Developmen-tal Neuroscience, 23:299–305.
22. Schwartz, DA. (2020). An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: maternal coronavirus infections and pregnancy outcomes. Arch Pathol Lab Med, doi: 10.5858/arpa.2020-0901-SA.
23. Katona P, Katona-Apte J (2008). The Interaction between Nutrition and Infection. Clin Infect Dis, 46(10):1582–8.
24. Castelo-Branco C, Soveral I (2014). The immune system and aging: a review. Gynecol Endocrinol, 30:16–22.
25. Gernand AD, Schulze KJ, Stewart CP, et al (2016). Micronutrient deﬁcien-cies in pregnancy worldwide: health effects and prevention. Nat Rev En-docrinol, 12(5):274–289.
26. Black RE (2001). Micronutrients in pregnancy. Br J Nutr, 85:S193–7.
27. Mccullough FS, Northropclewes CA, Thurnham DI (1999). The effect of vitamin A on epithelial integrity. Proc Nutr Soc, 58:289-93.
28. Huang Z, Liu Y, Qi G, et al (2018). Role of vitamin A in the immune system. J Clin Med, 7(9):258.
29. Mora JR, Iwata M, Von Andrian UH (2008). Vitamin effects on the im-mune system: vitamins A and D take centre stage. Nat Rev Immunol, 8:685-698.
30. Semba RD (1999). Vitamin A and im-munity to viral, bacterial and proto-zoan infections. Proc Nutr Soc, 58:719-27.
31. Spíndola Garcêz L, De Sousa Paz Lima G, de Azevedo Paiva A, et al (2016). Serum retinol levels in pregnant ado-lescents and their relationship with habitual food intake, infection and obstetric, nutritional and socioeco-nomic variables. Nutrients, 8(11):669.
32. Hammouda SA, Abd Al-Halim OA, Mohamadin AM (2013). Serum lev-els of some micronutrients and congenital malformations: A pro-spective cohort study in healthy Saudi-Arabian ﬁrst-trimester preg-nant women. Int J Vitam Nutr Res, 83:346–54.
33. Lakshmy R (2013). Metabolic syn-drome: Role of maternal undernutri-tion and fetal programming. Rev En-docr Metab Disord, 14(3):229–40.
34. Bao Y, Ibram G, Blaner WS, et al (2012). Low maternal retinol as a risk factor for schizophrenia in adult offspring. Schizophr Res, 137:159–165.
35. Lira LQ, Dimenstein R (2010). Vitamin A and gestational diabetes. Rev Assoc Med Bras, 56:355–9.
36. Huang Y, Zheng S (2011). The effect of vitamin A deﬁciency during preg-nancy on anorectal malformations. J Pediatr Surg, 46:1400–5.
37. Batista Filho M, Bastos Maia S, Rolland Souza AS, et al (2019). Vitamin A and pregnancy: A narrative review. Nutrients, 11(3):681.
38. Duerbeck NB, Dowling DD (2012). Vitamin A: too much of a good thing? Obstet Gynecol Surv, 67(2):122-8.
39. Harrison FE, Bowman GL, Polidori MC (2014). Ascorbic acid and the brain: rationale for the use against cognitive decline. Nutrients, 6(4):1752–1781.
40. Hemilä H (1992). Vitamin C and the common cold. Br J Nutr, 67:3–16.
41. Jafari D, Esmaeilzadeh A, Moham-madi-Kordkhayli M, et al (2019). Vitamin C and the Immune System. Nutrition and Immunity,81-102.
42. Hunt C, Chakravorty NK, Annan G, et al (1994). The clinical effects of vit-amin C supplementation in elderly hospitalised patients with acute res-piratory infections. Int J Vitam Nutr Res, 64(3):212–9.
43. Hemila H (2003). Vitamin C and SARS coronavirus. J Antimicrob Chemother, 52(6):1049-1050.
44. Hemila H (1997). Vitamin C intake and susceptibility to pneumonia. Pediatr Infect Dis J, 16(9):836-7.
45. Biondi C, Pavan B, Dalpiaz A, et al (2007). Expression and characteriza-tion of vitamin C transporter in the human trophoblast cell line HTR‑8/SVneo: Effect of steroids, flavonoids and NSAIDs. Mol Hum Reprod, 13(1): 77‑83.
46. Chen YH, Xu DX, Xhao L, et al (2006). Ascorbic acid protects against lipopolysaccharide‑induced intra‑uterine fetal death and in-tra‑uterine growth retardation in mice. Toxicology, 217:39‑45.
47. Hassan GI, Onu AB (2006). Total se-rum vitamin C concentration in pregnant women: Implications for a healthy pregnancy. Rev Bras Saude Mater Infant, 6:293‑296.
48. Kalaiselvi VS, Birundha S, Devi AJ, et al (2014). Estimation of ascorbic acid status in normal pregnancy. World Journal of Medical Sciences, 10 (2): 150-152.
49. Chappell LC, Seed PT, Kelly FJ, et al (2002). Vitamin C and E supple-mentation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function. Am J Obstet Gynecol, 187(3):777‑84.
50. Chappell LC, Seed PT, Briley AL, et al (1999). Effect of antioxidants on the occurrence of pre‑eclampsia in women at increased risk: A random-ised trial. Lancet, 354(9181):810-6.
51. Nonnecke BJ, McGill JL, Ridpath JF, et al (2014). Acute phase response elic-ited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E sta-tus of vitamin-replete preruminant calves. J Dairy Sci, 97(2):5566-79.
52. Urashima M, Segawa T, Okazaki M, et al (2010). Randomized trial of vita-min D supplementation to prevent seasonal influenza A in schoolchil-dren. Am J Clin Nutr, 91(5):1255–60.
53. Wei SQ (2014). Vitamin and pregnany outcomes. Curr Opin Obstet Gynecol, 26(6):438–47.
54. Bodnar LM, Catov JM, Simhan HN, et al (2007). Maternal vitamin D deﬁciency increases the risk of preeclampsia. J Clin Endocrinol Metab, 92(9):3517–3522.
55. Baker AM, Haeri S, Camargo CA Jr, et al (2010). A nested case-control study of midgestation vitamin D deﬁciency and risk of severe preeclampsia. J Clin Endocrinol Metab, 95(11):5105–5109.
56. Perez-Ferre N, Torrejon M, Fuentes M, et al (2012). Association of low se-rum 25-hydroxyvitamin D levels in pregnancy with glucose homeostasis and obstetric and newborn out-comes. Endocrine Practice, 18(5):676–84.
57. Bodnar LM, Simhan HN (2010). Vita-min D may be a link to Black-White disparities in adverse birth out-comes. Obstet Gynecol Surv, 65(4):273-84.
58. Leffelaar ER, Vrijkotte TG, van Eijsden M (2010). Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multi-ethnic Amsterdam Born Chil-dren and their Development cohort. Br J Nutr, 104(1):108–17.
59. Marjamäki L, Niinistö S, Kenward MG, et al (2010). Maternal intake of vita-min D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring. Diabeto-logia, 53(8):1599–1607.
60. Brehm JM, Celedón JC, Soto-Quiros ME, et al (2009). Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med, 179(9):765–71.
61. Stene LC, Ulriksen J, Magnus P, et al (2000). Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring. Diabetologia, 43(9):1093–8.
62. Carol LW, Bruce WH (2018). The Im-plications of Vitamin D Status Dur-ing Pregnancy on Mother and her Developing Child. Front Endocrinol (Lausanne), 9:500.
63. Lee GY, Han SN (2018). The Role of Vitamin E in Immunity. Nutrients, 10(11):1614.
64. Mosser DM, Edwards JP (2008). Ex-ploring the full spectrum of macro-phage activation. Nature Reviews Im-munology, 8:958–969.
65. Ravaglia G, Forti P, Maioli F, et al (2000). Effect of micronutrient sta-tus on natural killer cell immune function in healthy free-living sub-jects aged ≥90 y. Am J Clin Nutr, 71(2):590-8.
66. Tan PH, Sagoo P, Chan C, et al (2005). Inhibition of NF-kappa B and oxi-dative pathways in human dendritic cells by antioxidative vitamins gener-ates regulatory T cells. J Immunol, 174(12):7633-44.
67. Adolfsson O, Huber BT, Meydani SN (2001). Vitamin E-enhanced IL-2 production in old mice: Naive but not memory T cells show increased cell division cycling and IL-2-producing capacity. J Immunol, 167(7):3809-17.
68. Beharka AA, Han SN, Adolfsson O, et al (2000). Long-term dietary antioxi-dant supplementation reduces pro-duction of selected inﬂammatory mediators by murine macrophages. Nutrition Research, 20:281–296.
69. Han SN, Wu D, Ha WK, et al (2000). Vitamin E supplementation increas-es T helper 1 cytokine production in old mice infected with influenza vi-rus. Immunology, 100(4):487-493.
70. Hayek MG, Taylor SF, Bender BS, et al (1997). Vitamin E supplementation decreases lung virus titers in mice in-fected with inﬂuenza. J Infect Dis, 176(1):273–6.
71. Scholl TO, Leskiw M, Chen X, et al (2005). Oxidative stress, diet and the etiology of preeclampsia. Am J Clin Nutr, 81:1390–6.
72. Cave C, Hanson C, Schumacher M, et al (2018). A Comparison of Vitamin E Status and Associated Pregnancy Outcomes in Maternal–Infant Dy-ads between a Nigerian and a Unit-ed States Population. Nutrients, 10(9):1300.
73. Devereux G, Turner SW, Craig LC, et al (2006). Low maternal vitamin E intake during pregnancy is associat-ed with asthma in 5-year-old chil-dren. Am J Respir Crit Care Med, 174(5):499–507.
74. Fruscella L, Ciaglia EM, Danti M, et al (1997). [Vitamin E in the treatment of pregnancy complicated by uterine myoma]. Minerva Ginecol, 49(4):175-9.
75. Maggini S, Pierre A, Calder PC (2018). Immune Function and Micronutri-ent Requirements Change over the Life Course. Nutrients, 10(10):1531.
76. Haryanto B, Suksmasari T, Wintergerst E, et al (2015). Multivitamin supple-mentation supports immune func-tion and ameliorates conditions trig-gered by reduced air quality. Vitam Miner, 4:1–15.
77. Kuvibidila SR, Baliga SB, Chandra LC, et al (2013). The role of iron in im-munity and inflammation: implica-tions for the response to infection. Diet, Immunity and Inflammation, 193-220.
78. Oppenheimer SJ (2001). Iron, its rela-tion to immunity and infectious dis-ease. J Nutr, 131:616S–635S.
79. Osendarp SJM, Murray-Kolb LE, Black MM (2010). Case study on iron in mental development – in memory of John Beard (1947–2009). Nutr Rev, 68:S48-S52.
80. Stevens GA, Finucane MM, De-Regil LM, et al (2013). Global, regional, and national trends in haemoglobin concentration and prevalence of to-tal and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data. Lancet Glob Health, 1:e16–25.
81. Hovdenak N, Haram K (2012). Influ-ence of mineral and vitamin sup-plements on pregnancy outcomes. Eur J Obstet Gynecol Reprod Biol, 164(2):127–32.
82. Huang Z, Rose AH, Hoffmann PR (2012). The role of selenium in inﬂammation and immunity: From molecular mechanisms to therapeu-tic opportunities. Antioxid Redox Sig-nal, 16(7): 705–743.
83. Joseph C, Avery ID, Hoffmann PR (2018). Selenium, Selenoproteins, and Immunity. Nutrients, 10(9): 1203.
84. Beck MA, Nelson HK, Shi Q, et al (2001). Selenium deﬁciency increases the pathology of an inﬂuenza virus infection. FASEB J, 15(8):1481-3.
85. Gill H, Walker G (2008). Selenium, im-mune function and resistance to vi-ral infections. Nutrition & Dietetics, 65:S41–S47.
86. Tapiero H, Townsend DM, Tew KD (2003). The antioxidant role of sele-nium and seleno-compounds. Bio-med. Biomed Pharmacother, 57:134–144.
87. Fialova L, Malbohan I, Kalousova M, et al (2006). Oxidative stress and inﬂammation in pregnancy. Scand J Clin Lab Invest, 66(2):121-7.
88. Mistry HD, Pipkin FB, Redman CW, et al (2012). Selenium in reproductive health. Am J Obstet Gynecol, 206(1):21-30.
89. Rayman MP, Bode P, Redman CW (2003). Low selenium status is asso-ciated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom. Am J Obstet Gynecol, 189(5):1343-9.
90. Nawrot TS, Staessen JA, Roels HA, et al (2007). Blood pressure and blood selenium: a cross-sectional and lon-gitudinal population study. Eur Heart J, 28(5):628-33.
91. Shankar AH, Prasad AS (1998). Zinc and immune function: the biological basis of altered resistance to infec-tion. Am J Clin Nutr, 68:447S–463S.
92. Bonaventura P, Benedetti G, Albarède F, et al (2015). Zinc and its role in immunity and inflammation. Auto-immun Rev, 14(4):277-85.
93. Sazawal S, Black R, Jalla S, et al (1998). Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind controlled trial. Pediatrics, 102:1–5.
94. Te Velthuis AJ, van den Worm SH, Sims AC, et al (2010). Zn(2+) inhib-its coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog, 6(11): e1001176.
95. King J (2000). Physiology of pregnancy and nutrient metabolism. Am J Clin Nut, 71:1218S-25S.
96. King J (2011). Zinc: an essential but elusive nutrient. Am J Clin Nutr, 94(2): 679S–684S.
97. Caulfield L, Zavaleta N, Shankar A, et al (1998). Potential contribution of maternal zinc supplementation dur-ing pregnancy to maternal and child survival. Am J Clin Nutr, 68:499S-508S.
98. Mistry H, Williams P (2011). The im-portance of antioxidant micronutri-ents in pregnancy. Oxid Med Cell Longev, 2011: 841749.
99. Pe~na-Rosas JP, De-Regil LM, Dow-swell T, et al (2015). Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev, 22;(7):CD004736.
100. Dietary Reference Intakes for Vita-min A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2001) Food and Nutrition Board (FNB) Institute of Medicine (IOM)2001 http://www.nap.edu/catalog.php?record_id=10026
101. Dietary Reference Intakes for Calcium, Phosphorous, Magnesium, Vitamin D, and Fluoride (1997); http://www.nap.edu/catalog.php?record_id=5776
102. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998); Dietary Reference In-takes for Vitamin C, Vitamin E, Selenium, and Carotenoids (2000); http://www.nap.edu/catalog.php?record_id=6015
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|COVID-19 Micronutrients Immune function Pregnancy outcomes|
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