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Review

Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D

1
Division of Infectious Disease, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
2
Division of Nephrology, Department of Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan
3
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
4
Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
5
Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
6
Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
7
Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 234, Taiwan
8
Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei 110, Taiwan
9
Division of Nephrology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, New Taipei City 235, Taiwan
10
Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
11
Division of Cardiovascular Surgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
12
School of Medicine, Tzu Chi University, Hualien 970, Taiwan
13
Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
14
Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Maurizio Battino
Int. J. Mol. Sci. 2021, 22(10), 5251; https://doi.org/10.3390/ijms22105251
Received: 10 April 2021 / Revised: 30 April 2021 / Accepted: 12 May 2021 / Published: 16 May 2021
(This article belongs to the Collection Feature Papers in Bioactives and Nutraceuticals)
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. View Full-Text
Keywords: coronavirus disease 2019; severe acute respiratory syndrome coronavirus 2; vitamin D; adaptive immunity; innate immunity; angiotensin-converting enzyme 2; renin–angiotensin–aldosterone system coronavirus disease 2019; severe acute respiratory syndrome coronavirus 2; vitamin D; adaptive immunity; innate immunity; angiotensin-converting enzyme 2; renin–angiotensin–aldosterone system
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MDPI and ACS Style

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. Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. Int. J. Mol. Sci. 2021, 22, 5251. https://doi.org/10.3390/ijms22105251

AMA Style

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. Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. International Journal of Molecular Sciences. 2021; 22(10):5251. https://doi.org/10.3390/ijms22105251

Chicago/Turabian Style

Peng, Ming-Yieh, Wen-Chih Liu, Jing-Quan Zheng, Chien-Lin Lu, Yi-Chou Hou, Cai-Mei Zheng, Jenn-Yeu Song, Kuo-Cheng Lu, and You-Chen Chao. 2021. "Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D" International Journal of Molecular Sciences 22, no. 10: 5251. https://doi.org/10.3390/ijms22105251

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