Role of vitamin D in regulating COVID-19 severity—An immunological perspective

Kalia, Vandana; Studzinski, George P.; Sarkar, Surojit

doi:10.1002/jlb.4covr1020-698r

Cited by 24 publications

(12 citation statements)

References 190 publications

(364 reference statements)

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“…The ability to metabolise 25D to 1,25D has also been described for normal healthy monocytes/macrophages ( 22 ), which show enhanced expression of the genes for 1α-hydroxylase ( CYP27B1) , and VDR following immune stimulation ( 23 ). The resulting endogenous synthesis and action of 1,25D have been shown to promote antibacterial ( 24 , 25 ), and antiviral ( 26 , 27 ) innate immune responses to infection. The cell-specific nature of these responses, utilising endogenous 1α-hydroxylase activity, means that local levels of 25D rather than active 1,25D, are likely to be the primary determinant of vitamin D-mediated innate immune responses.…”

Section: Vitamin D Innate Immunity and Antigen Presentationmentioning

confidence: 99%

Autoimmune disease and interconnections with vitamin D

Fletcher

Bishop

Harrison

et al. 2022

Endocrine Connections

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Vitamin D has well documented effects on calcium homeostasis and bone metabolism but recent studies suggest a much broader role for this secosteroid in human health. Key components of the vitamin D system, notably the vitamin D receptor (VDR) and the vitamin D activating enzyme (1α-hydroxylase), are present in a wide array of tissues, notably macrophages, dendritic cells and T lymphocytes (T cells) from the immune system. Thus, serum 25-hydroxyvitamin D (25D) can be converted to hormonal 1,25-dihydroxyvitamin D (1,25D) within immune cells, and then interact with VDR and promote transcriptional and epigenomic responses in the same or neighbouring cells. These intracrine and paracrine effects of 1,25D have been shown to drive antibacterial or antiviral innate responses, as well as attenuating inflammatory T cell adaptive immunity. Beyond these mechanistic observations, association studies have reported correlation between low serum 25D levels and the risk and severity of human immune disorders including autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, type 1 diabetes and rheumatoid arthritis. The proposed explanation for this is that decreased availability of 25D compromises immune cell synthesis of 1,25D leading to impaired innate immunity and over-exuberant inflammatory adaptive immunity. The aim of the current review is to explore the mechanistic basis for immunomodulatory effects of 25D and 1,25D in greater detail with specific emphasis on how vitamin D-deficiency (low serum levels of 25D) may lead to dysregulation of macrophage, dendritic cell and T cell function, and increase risk of inflammatory autoimmune disease.

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Section: Vitamin D Innate Immunity and Antigen Presentationmentioning

confidence: 99%

Autoimmune disease and interconnections with vitamin D

Fletcher

Bishop

Harrison

et al. 2022

Endocrine Connections

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“…Vitamin D deficiency has been associated with risk for the development of COVID-19 and its deficiency must be corrected 138 ; its effect on immune dynamics is postulated, 139 however its effect as a TF inhibitor has yet to be demonstrated. Recent reviews speculate on the usefulness of antioxidants 140,141 and selenium.…”

Section: Tf Inhibition In Covid-19mentioning

confidence: 99%

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

Cañas

Cañas²,

Bautista-Vargas

et al. 2021

Clin Appl Thromb Hemost

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COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.

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“…The receptor was expressed in immune cells, including T cells (CD4+ and CD8+), B cells, and antigen-presenting cells (macrophages and dendritic cells). Vitamin D can decrease pro-inflammatory cytokines by regulating macrophages and activity of T lymphocytes, such as expansion and migration of T cells in the lung during SARS-Cov-2 infection [36,37]. Vitamin D can up-regulate the regulatory type-2 (T-reg) cells and reduce expression of Th17-stimulating cytokines.…”

Section: Discussionmentioning

confidence: 99%

Serum Vitamin D levels in pediatric patients and its association with COVID-19 clinical manifestation: A meta-analysis and systematic review

Jonatan¹,

Setyoningrum²

2021

GSC Biol. and Pharm. Sci.

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Background: Vitamin D is involved in human immune system homeostasis and thought to be beneficial for COVID-19 patients, including pediatric population. However, there is still a paucity of information on association of serum vitamin D levels and COVID-19 clinical manifestation in pediatric patients. This study evaluated the association between serum vitamin D levels and clinical manifestations of COVID-19 in pediatric patients. Methods: We searched PubMed and Google Scholar for articles reporting association between vitamin D and COVID-19 clinical manifestations in pediatric patients. We searched for English-written articles only. PRISMA-MOOSE guideline and quality checklist was complied and statistical analysis was performed using RevMan 5.4. Results: Ten studies with total of 1,225 patients reported were reviewed. Low vitamin D levels was significantly associated with higher incidence of severe COVID-19 with pooled OR was 5.57 (1.59-19.55; p=0.007). Clinical symptoms were compared between low and normal vitamin D levels. Incidence of fever, cough, ageusia, anosmia, headache, and fatigue were not significantly different between group, with pooled RR was 2.13 (0.13-33.73; p=0.59), 1.25 (0.25-6.22; p=0.78), 0.47 (0.05-4.76; p=0.52), 1.25 (0.21-7.41; p=0.81), 0.91 (0.33-2.55; p=0.86), and 1.02 (0.47-2.22; p=0.96), respectively. The mean count of leukocytes and lymphocytes in the two groups were also not significantly different with pooled RR was -0.49 (-1.39-0.41; p=0.28), and -0.73 (-1.65-0.20; p=0.12), respectively. Conclusion: Low serum vitamin D level (<20 ng/ml) is associated with the severity of COVID-19 in pediatric patients, but do not affect symptoms and laboratory parameters. Vitamin D supplementation might be beneficial for children undergo medical quarantine and isolation.

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Role of vitamin D in regulating COVID-19 severity—An immunological perspective

Cited by 24 publications

References 190 publications

Autoimmune disease and interconnections with vitamin D

Autoimmune disease and interconnections with vitamin D

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

Serum Vitamin D levels in pediatric patients and its association with COVID-19 clinical manifestation: A meta-analysis and systematic review

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