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Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D.
Int J Mol Sci. 2021 May 16; 22(10)IJ

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and β-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4+ T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4+ T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin-angiotensin-aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill's causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19.

Authors+Show Affiliations

Division of Infectious Disease, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.Division of Nephrology, Department of Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan.Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 234, Taiwan.Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei 110, Taiwan. Division of Nephrology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, New Taipei City 235, Taiwan. Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.Division of Cardiovascular Surgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan. School of Medicine, Tzu Chi University, Hualien 970, Taiwan.Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.School of Medicine, Tzu Chi University, Hualien 970, Taiwan. Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

34065735

Citation

Peng, Ming-Yieh, et al. "Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D." International Journal of Molecular Sciences, vol. 22, no. 10, 2021.
Peng MY, Liu WC, Zheng JQ, et al. Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. Int J Mol Sci. 2021;22(10).
Peng, M. Y., Liu, W. C., Zheng, J. Q., Lu, C. L., Hou, Y. C., Zheng, C. M., Song, J. Y., Lu, K. C., & Chao, Y. C. (2021). Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. International Journal of Molecular Sciences, 22(10). https://doi.org/10.3390/ijms22105251
Peng MY, et al. Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. Int J Mol Sci. 2021 May 16;22(10) PubMed PMID: 34065735.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. AU - Peng,Ming-Yieh, AU - Liu,Wen-Chih, AU - Zheng,Jing-Quan, AU - Lu,Chien-Lin, AU - Hou,Yi-Chou, AU - Zheng,Cai-Mei, AU - Song,Jenn-Yeu, AU - Lu,Kuo-Cheng, AU - Chao,You-Chen, Y1 - 2021/05/16/ PY - 2021/04/10/received PY - 2021/04/30/revised PY - 2021/05/12/accepted PY - 2021/6/2/entrez PY - 2021/6/3/pubmed PY - 2021/6/3/medline KW - adaptive immunity KW - angiotensin-converting enzyme 2 KW - coronavirus disease 2019 KW - innate immunity KW - renin–angiotensin–aldosterone system KW - severe acute respiratory syndrome coronavirus 2 KW - vitamin D JF - International journal of molecular sciences JO - Int J Mol Sci VL - 22 IS - 10 N2 - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and β-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4+ T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4+ T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin-angiotensin-aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill's causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/34065735/Immunological_Aspects_of_SARS_CoV_2_Infection_and_the_Putative_Beneficial_Role_of_Vitamin_D_ L2 - https://www.mdpi.com/resolver?pii=ijms22105251 DB - PRIME DP - Unbound Medicine ER -