Correlation between premorbid IL-6 levels and COVID-19 mortality: Potential role for Vitamin D

Silberstein, Morry

doi:10.1016/j.intimp.2020.106995

Cited by 36 publications

(32 citation statements)

References 45 publications

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“…Acute respiratory distress syndrome in COVID-19 infection is thought to be secondary to dysregulation of the immune system. Several authors have highlighted abnormally high levels of proinflammatory cytokines in patients developing severe forms of COVID-19 infection with pulmonary involvement and acute respiratory distress [9,10,37]. Some authors have suggested that vitamin D could be active on the immune and respiratory systems [38], notably by modulating cytokine production [13].…”

Section: Discussionmentioning

confidence: 99%

“…Respiratory distress most often occurs more than seven days after the onset of symptoms [5] and is frequently observed in aged people [6][7][8]. Several authors have demonstrated abnormally high levels of proinflammatory cytokines in patients developing severe forms of COVID-19 infection [9,10]. In light of this, it has been suggested that the respiratory complications of COVID-19 infection occurring beyond day seven were due to a dysregulation of the immune system, termed the "cytokine storm" [11].…”

Section: Introductionmentioning

confidence: 99%

“…Activated vitamin D is involved at different immune response levels [12], notably by activating innate immunity and reducing overactivation of the adaptive immune system [13]. Vitamin D administration may lower interleukin-6 levels [10]. In 2009, Grant et al [14] suggested a possible vitamin D role in reducing casefatality rates from the 1918-1919 influenza pandemic.…”

Section: Introductionmentioning

confidence: 99%

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Relation between Vitamin D and COVID-19 in Aged People: A Systematic Review

Dramé

Cofais²,

Hentzien

et al. 2021

Nutrients

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Background: Vitamin D has diverse and extensive effects on the immune system, including activating innate immunity and reducing the overactive adaptive immune response. A systematic review was performed to identify and synthesize the best available evidence on the association between vitamin D level and risk of COVID-19, adverse outcomes and possible benefits of supplementation in aged 60 years or over. Methods: A literature search was performed in PubMed© and Scopus© for all publications from inception published before 15 March 2021. Studies reporting data from aged patients on vitamin D use and COVID-19 were included. Basic science articles, editorials and correspondence were excluded. Publication year, study design and setting, characteristics of the study population were extracted. This study is registered with PROSPERO, under the number CRD42020223993. Results: In total, 707 studies were identified, of which 11 observational studies were included in the final review. Four studies compared vitamin D-supplemented COVID-19 patients to non-supplemented patients, and seven compared patients with vitamin D deficiency to patients without deficiency. In all four studies, patients with vitamin D supplementation had better rates of primary clinical outcomes (death, the severity of the disease, oxygen therapy requirement…). In studies comparing patients with vitamin D deficiency and patients without vitamin D deficiency, those without vitamin D deficiency had better primary clinical outcomes (death rate, the severity of the disease, oxygen therapy requirement, invasive mechanical ventilation need…). Conclusion: This systematic review seems to support an association between vitamin D deficiency and the risk of COVID-19 in aged people. In addition, vitamin D deficiency appears to expose these subjects to a greater risk of adverse outcomes. Because of its simplicity of administration, and the rarity of side effects, including vitamin D in preventive strategies for certain viral diseases, it appears to be an attractive option.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relation between Vitamin D and COVID-19 in Aged People: A Systematic Review

Dramé

Cofais²,

Hentzien

et al. 2021

Nutrients

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“…Contrast this with Vitamin D, which lowers immune cell IL-6 production ( Silberstein, 2020a ), potentially reducing pro-inflammatory effects, but does not specifically target IL-6 receptors, avoiding any deleterious effect on the anti-inflammatory actions of IL-6. Vitamin D has also been shown to lower TNF levels ( Peterson and Heffernan, 2008 ), representing an additional therapeutic mechanism for countering the COVID-19 cytokine storm.…”

Section: Discussionmentioning

confidence: 99%

“…Vitamin D, which has immunomodulatory properties (Sassi et al, 2020), was proposed as a potential therapeutic option in the early part of the pandemic ( Silberstein, 2020b ), supported in part by reports of Vitamin D deficiency resulting in poorer outcomes (see the review by Benskin, 2020 ). Yet, despite calls for clinical trials of this vitamin ( Silberstein, 2020b ), in part based upon its modulation of IL-6, a key interleukin implicated in viral replication ( Silberstein, 2020a ), only a few have been completed at time of writing. This comes as a surprise, given the widespread promotion and multiple trials of the IL-6 antagonist tocilizumab ( Tleyjeh et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

COVID-19 and IL-6: Why vitamin D (probably) helps but tocilizumab might not

Silberstein

2021

European Journal of Pharmacology

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Interleukin 6 (IL-6), which is involved in the cytokine storm phenomenon, is a therapeutic target in COVID-19, but monoclonal receptor antibody therapeutic agents such as tocilizumab have demonstrated mixed results. Could Vitamin D, which modulates IL-6, be more effective than currently deployed IL-6 antagonists, including tocilizumab, thereby presenting a useful therapeutic option in COVID-19? A narrative review of published trials examining the effect of Vitamin D administration in COVID-19 patients was conducted, and the theoretical basis for the use of tocilizumab as an IL-6 antagonist was compared with the immunomodulatory effect of Vitamin D on IL-6 production. Four of the six included studies reported a positive effect of Vitamin D on outcomes. While tocilizumab non-selectively blocks both anti-inflammatory and pro-inflammatory actions of IL-6, Vitamin D lowers immune cell IL-6 production, potentially reducing pro-inflammatory effects, but does not specifically target IL-6 receptors, avoiding any deleterious effect on the anti-inflammatory actions of IL-6. Vitamin D may have advantages over tocilizumab as an IL-6 immunomodulator, and, given that it is safe if administered under clinical supervision, there is a strong rationale for its use.

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Vitamin D, infections and immunity

Ismailova

White

2021

Rev Endocr Metab Disord

172

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Vitamin D, best known for its role in skeletal health, has emerged as a key regulator of innate immune responses to microbial threat. In immune cells such as macrophages, expression of CYP27B1, the 25-hydroxyvitamin D 1α-hydroxylase, is induced by immune-specific inputs, leading to local production of hormonal 1,25-dihydroxyvitamin D (1,25D) at sites of infection, which in turn directly induces the expression of genes encoding antimicrobial peptides. Vitamin D signaling is active upstream and downstream of pattern recognition receptors, which promote front-line innate immune responses. Moreover, 1,25D stimulates autophagy, which has emerged as a mechanism critical for control of intracellular pathogens such as M. tuberculosis. Strong laboratory and epidemiological evidence links vitamin D deficiency to increased rates of conditions such as dental caries, as well as inflammatory bowel diseases arising from dysregulation of innate immune handling intestinal flora. 1,25D is also active in signaling cascades that promote antiviral innate immunity; 1,25D-induced expression of the antimicrobial peptide CAMP/LL37, originally characterized for its antibacterial properties, is a key component of antiviral responses. Poor vitamin D status is associated with greater susceptibility to viral infections, including those of the respiratory tract. Although the severity of the COVID-19 pandemic has been alleviated in some areas by the arrival of vaccines, it remains important to identify therapeutic interventions that reduce disease severity and mortality, and accelerate recovery. This review outlines of our current knowledge of the mechanisms of action of vitamin D signaling in the innate immune system. It also provides an assessment of the therapeutic potential of vitamin D supplementation in infectious diseases, including an up-to-date analysis of the putative benefits of vitamin D supplementation in the ongoing COVID-19 crisis.

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Correlation between premorbid IL-6 levels and COVID-19 mortality: Potential role for Vitamin D

Cited by 36 publications

References 45 publications

Relation between Vitamin D and COVID-19 in Aged People: A Systematic Review

Relation between Vitamin D and COVID-19 in Aged People: A Systematic Review

COVID-19 and IL-6: Why vitamin D (probably) helps but tocilizumab might not

Vitamin D, infections and immunity

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