Vitamin D and COVID-19: Role of ACE2, Age, Gender, and Ethnicity

Overview

Journal J Med Virol

Specialty Microbiology

Date 2021 May 15

PMID 33990955

Citations 32

Authors

Bruk Getachew

Yousef Tizabi

Affiliations

Soon will be listed here.

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, disproportionally targets older people, particularly men, ethnic minorities, and individuals with underlying diseases such as compromised immune system, cardiovascular disease, and diabetes. The discrepancy in COVID-19 incidence and severity is multifaceted and likely involves biological, social, as well as nutritional status. Vitamin D deficiency, notably common in Black and Brown people and elderly, is associated with an increased susceptibility to many of the diseases comorbid with COVID-19. Vitamin D deficiency can cause over-activation of the pulmonary renin-angiotensin system (RAS) leading to the respiratory syndrome. RAS is regulated in part at least by angiotensin-converting enzyme 2 (ACE2), which also acts as a primary receptor for SARS-CoV-2 entry into the cells. Hence, vitamin D deficiency can exacerbate COVID-19, via its effects on ACE2. In this review we focus on influence of age, gender, and ethnicity on vitamin D-ACE2 interaction and susceptibility to COVID-19.

Citing Articles

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References

Malek Mahdavi A . A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19. Rev Med Virol. 2020; 30(5):e2119. PMC: 7362103. DOI: 10.1002/rmv.2119. View

Dielis A, Smid M, Spronk H, Hamulyak K, Kroon A, Ten Cate H . The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems. Hypertension. 2005; 46(6):1236-42. DOI: 10.1161/01.HYP.0000193538.20705.23. View

Dowd J, Aiello A . Socioeconomic differentials in immune response. Epidemiology. 2009; 20(6):902-8. PMC: 2765221. DOI: 10.1097/EDE.0b013e3181bb5302. View

Townsend K, Evans K, Campbell M, Colston K, Adams J, Hewison M . Biological actions of extra-renal 25-hydroxyvitamin D-1alpha-hydroxylase and implications for chemoprevention and treatment. J Steroid Biochem Mol Biol. 2005; 97(1-2):103-9. DOI: 10.1016/j.jsbmb.2005.06.004. View

Wu Z, McGoogan J . Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13):1239-1242. DOI: 10.1001/jama.2020.2648. View

Tukiainen T, Villani A, Yen A, Rivas M, Marshall J, Satija R . Landscape of X chromosome inactivation across human tissues. Nature. 2017; 550(7675):244-248. PMC: 5685192. DOI: 10.1038/nature24265. View

Tomaschitz A, Pilz S, Ritz E, Grammer T, Drechsler C, Boehm B . Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin Chim Acta. 2010; 411(17-18):1354-60. DOI: 10.1016/j.cca.2010.05.037. View

Spanier J, Nashold F, Mayne C, Nelson C, Hayes C . Vitamin D and estrogen synergy in Vdr-expressing CD4(+) T cells is essential to induce Helios(+)FoxP3(+) T cells and prevent autoimmune demyelinating disease. J Neuroimmunol. 2015; 286:48-58. DOI: 10.1016/j.jneuroim.2015.06.015. View

Regitz-Zagrosek V, Oertelt-Prigione S, Seeland U, Hetzer R . Sex and gender differences in myocardial hypertrophy and heart failure. Circ J. 2010; 74(7):1265-73. DOI: 10.1253/circj.cj-10-0196. View

10.

Zhang S, Tuo J, Huang X, Zhu X, Zhang D, Zhou K . Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou. PLoS One. 2018; 13(1):e0191789. PMC: 5788356. DOI: 10.1371/journal.pone.0191789. View

11.

Choudhary S, Sreenivasulu K, Mitra P, Misra S, Sharma P . Role of Genetic Variants and Gene Expression in the Susceptibility and Severity of COVID-19. Ann Lab Med. 2020; 41(2):129-138. PMC: 7591285. DOI: 10.3343/alm.2021.41.2.129. View

12.

Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong J, Turner A . Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circ Res. 2020; 126(10):1456-1474. PMC: 7188049. DOI: 10.1161/CIRCRESAHA.120.317015. View

13.

Kaufman H, Niles J, Kroll M, Bi C, Holick M . SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One. 2020; 15(9):e0239252. PMC: 7498100. DOI: 10.1371/journal.pone.0239252. View

14.

Bukowska A, Spiller L, Wolke C, Lendeckel U, Weinert S, Hoffmann J . Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men. Exp Biol Med (Maywood). 2017; 242(14):1412-1423. PMC: 5544171. DOI: 10.1177/1535370217718808. View

15.

Grant W, Baggerly C, Lahore H . Reply: "Vitamin D Supplementation in Influenza and COVID-19 Infections. Comment on: Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths 2020, (4), 988". Nutrients. 2020; 12(6). PMC: 7352449. DOI: 10.3390/nu12061620. View

16.

Jaillon S, Berthenet K, Garlanda C . Sexual Dimorphism in Innate Immunity. Clin Rev Allergy Immunol. 2017; 56(3):308-321. DOI: 10.1007/s12016-017-8648-x. View

17.

Grant W, Peiris A . Possible role of serum 25-hydroxyvitamin D in black-white health disparities in the United States. J Am Med Dir Assoc. 2010; 11(9):617-28. DOI: 10.1016/j.jamda.2010.03.013. View

18.

Tangpricha V, Pearce E, Chen T, Holick M . Vitamin D insufficiency among free-living healthy young adults. Am J Med. 2002; 112(8):659-62. PMC: 3091001. DOI: 10.1016/s0002-9343(02)01091-4. View

19.

Chen Y, Zhang P, Zhou X, Liu D, Zhong J, Zhang C . Relationship between genetic variants of ACE2 gene and circulating levels of ACE2 and its metabolites. J Clin Pharm Ther. 2017; 43(2):189-195. DOI: 10.1111/jcpt.12625. View

20.

Xiao D, Li X, Su X, Mu D, Qu Y . Could SARS-CoV-2-induced lung injury be attenuated by vitamin D?. Int J Infect Dis. 2020; 102:196-202. PMC: 7591873. DOI: 10.1016/j.ijid.2020.10.059. View