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Vitamin D and COVID-19: A review on the role of vitamin D in preventing and reducing the severity of COVID-19 infection.
Abdrabbo, M, Birch, CM, Brandt, M, Cicigoi, KA, Coffey, SJ, Dolan, CC, Dvorak, H, Gehrke, AC, Gerzema, AEL, Hansen, A, et al
Protein science : a publication of the Protein Society. 2021;(11):2206-2220
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Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a pathogenic coronavirus causing COVID-19 infection. The interaction between the SARS-CoV-2 spike protein and the human receptor angiotensin-converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide-thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID-19. However, the molecular-level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID-19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID-19 infection or reducing the severity of the disease.
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Oral high dose vitamin D for the treatment of diabetic patients with COVID-19: A protocol for systematic review and meta-analysis.
Nie, X, Chen, J, Ye, F, Wang, H, Tang, L, Wang, L
Medicine. 2021;(9):e24517
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Abstract
BACKGROUND Type 2 diabetes mellitus patients complicated with infections experience severe vitamin D deficiency. High-dose vitamin D is applied to the treatment of corona virus disease 2019 (COVID-19) by some researchers, and good results have been achieved. However, the efficacy of vitamin D in the treatment of infections in COVID-19 patients with diabetes remains unclarified. This study aims to explore the effect of oral high-dose vitamin D in the treatment of diabetic patients with COVID-19. METHODS Randomized controlled trials about the application of high-dose vitamin D in the treatment of diabetic patients with COVID-19 will be retrieved from such electronic databases as Embase, PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure database, Chinese Wanfang database and Chinese Biomedical Literature database. The retrieval time is from their inception to December 2020. According to the pre-designed inclusion/exclusion criteria, the data will be extracted independently by two researchers. The risk of bias of the included studies will be assessed by the Cochrane collaboration's tool. Meta-analysis will be conducted by using Revman 5.3 software. RESULTS A high-quality and comprehensive evaluation of oral high-dose vitamin D for the treatment of diabetic patients with COVID-19 will be made. CONCLUSION The article will provide more convincing evidence and evidence-based guidance for clinical practice. ETHICS AND DISSEMINATION The private information of individuals will not be made public, and this systematic evaluation will also not infringe on the rights of participants. Ethical approval is not required. Research results may be published in a peer-reviewed journal or disseminated in relevant conferences. PROSPERO REGISTRATION NUMBER CRD42020214284.
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"Vitamin D supplementation and COVID-19 treatment: A systematic review and meta-analysis".
Rawat, D, Roy, A, Maitra, S, Shankar, V, Khanna, P, Baidya, DK
Diabetes & metabolic syndrome. 2021;(4):102189
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BACKGROUND Vitamin-D is an immune-modulator which might be linked to disease severity by SARS-CoV-2. METHODS Meta-analysis of RCTs and quasi-experimental studies, evaluating the role of vitamin-D supplementation in COVID patients was done. RESULTS Total 5 studies (3 RCTs and 2 Quasi-experimental) including n = 467 patients were included. Vitamin D didn't reduce mortality (RR 0.55, 95%CI 0.22 to 1.39, p = 0.21), ICU admission rates (RR 0.20, 95% CI 0.01-4.26, p = 0.3) and need for invasive ventilation (RR 0.24, 95% CI 0.01-7.89, p = 0.42). CONCLUSION No significant difference with vitamin-D supplementation on major health related outcomes in COVID-19. Well-designed RCTs are required addressing this topic.
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Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients.
Loucera, C, Peña-Chilet, M, Esteban-Medina, M, Muñoyerro-Muñiz, D, Villegas, R, Lopez-Miranda, J, Rodriguez-Baño, J, Túnez, I, Bouillon, R, Dopazo, J, et al
Scientific reports. 2021;(1):23380
Abstract
COVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15-30 days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan-Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95% confidence interval, CI, of [0.50-0.91]) than for cholecalciferol (HR = 0.75, with 95% CI of [0.61-0.91]), when prescribed 15 days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30 days prior hospitalization is considered (calcifediol HR = 0.73, with 95% CI [0.57-0.95] and cholecalciferol HR = 0.88, with 95% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization.
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COVID-19 and IL-6: Why vitamin D (probably) helps but tocilizumab might not.
Silberstein, M
European journal of pharmacology. 2021;:174031
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Abstract
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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Can Optimum Solar Radiation Exposure or Supplemented Vitamin D Intake Reduce the Severity of COVID-19 Symptoms?
Abraham, J, Dowling, K, Florentine, S
International journal of environmental research and public health. 2021;(2)
Abstract
The foremost mortality-causing symptom associated with COVID-19 is acute respiratory distress syndrome (ARDS). A significant correlation has been identified between the deficiency in vitamin D and the risk of developing ARDS. It has been suggested that if we can reduce or modify ARDS in COVID-19 patients, we may significantly reduce the severity of COVID-19 symptoms and associated mortality rates. The increased mortality of dark-skinned people, who have a reduced UV absorption capacity, may be consistent with diminished vitamin D status. The factors associated with COVID-19 mortality, such as old age, ethnicity, obesity, hypertension, cardiovascular diseases, and diabetes, are all found to be linked with vitamin D deficiency. Based on this review and as a precautionary measure, it is suggested that the adoption of appropriate and safe solar exposure and vitamin D enriched foods and supplements should be considered to reduce the possible severity of COVID-19 symptoms. Safe sun exposure is deemed beneficial globally, specifically in low and middle-income countries, as there is no cost involved. It is also noted that improved solar exposure and vitamin D levels can reduce the impact of other diseases as well, thus assisting in maintaining general human well-being.
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Supplementation with vitamin D in the COVID-19 pandemic?
Hadizadeh, F
Nutrition reviews. 2021;(2):200-208
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic was declared a public health emergency of international concern by the World Health Organization. COVID-19 has high transmissibility and could result in acute lung injury in a fraction of patients. By counterbalancing the activity of the renin-angiotensin system, angiotensin-converting enzyme 2, which is the fusion receptor of the virus, plays a protective role against the development of complications of this viral infection. Vitamin D can induce the expression of angiotensin-converting enzyme 2 and regulate the immune system through different mechanisms. Epidemiologic studies of the relationship between vitamin D and various respiratory infections were reviewed and, here, the postulated mechanisms and clinical data supporting the protective role of vitamin D against COVID-19-mediated complications are discussed.
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Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc.
Corrao, S, Mallaci Bocchio, R, Lo Monaco, M, Natoli, G, Cavezzi, A, Troiani, E, Argano, C
Nutrients. 2021;(4)
Abstract
More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.
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Inositol and vitamin D may naturally protect human reproduction and women undergoing assisted reproduction from Covid-19 risk.
Bezerra Espinola, MS, Bertelli, M, Bizzarri, M, Unfer, V, Laganà, AS, Visconti, B, Aragona, C
Journal of reproductive immunology. 2021;:103271
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Abstract
In late 2019, the new Coronavirus has been identified in the city of Wuhan then COVID-19 spreads like wildfire in the rest of the world. Pregnant women represent a risk category for increased abortion rates and vertical transmission with adverse events on the newborns has been recently confirmed. The scientific world is struggling for finding an effective cure for counteracting symptomatology. Today, there are many therapeutic proposes but none of them can effectively counteract the infection. Moreover, many of these compounds show important side effects not justifying their use. Scientific literature reports an immune system over-reaction through interleukins-6 activation. In this regard, the possibility to control the immune system represents a possible strategy for counteracting the onset of COVID-19 symptomatology. Vitamin D deficiency shows increased susceptibility to acute viral respiratory infections. Moreover, Vitamin D seems involved in host protection from different virus species by modulating activation and release of cytokines. Myo-inositol down-regulates the expression of IL-6 by phosphatidyl-inositol-3-kinase (PI3K) pathway. Furthermore, myo-inositol is the precursor of phospholipids in the surfactant and it is applied for inducing surfactant synthesis in infants for treating respiratory distress syndrome (RDS). This review aims to summarize the evidence about COVID-19 infection in pregnant women and to encourage the scientific community to investigate the use of Vitamin D and Myo-inositol which could represent a possible preventive treatment for pregnant women or women undergoing assisted reproductive technologies (ART).
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Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease.
Lakkireddy, M, Gadiga, SG, Malathi, RD, Karra, ML, Raju, ISSVPM, Ragini, , Chinapaka, S, Baba, KSSS, Kandakatla, M
Scientific reports. 2021;(1):10641
Abstract
COVID 19 is known to cause immune dysregulation and vitamin D is a known immunomodulator. This study aims to objectively investigate the impact of Pulse D therapy in reducing the inflammatory markers of COVID-19. Consented COVID-19 patients with hypovitaminosis D were evaluated for inflammatory markers (N/L ratio, CRP, LDH, IL6, Ferritin) along with vitamin D on 0th day and 9th/11th day as per their respective BMI category. Subjects were randomised into VD and NVD groups. VD group received Pulse D therapy (targeted daily supplementation of 60,000 IUs of vitamin D for 8 or 10 days depending upon their BMI) in addition to the standard treatment. NVD group received standard treatment alone. Differences in the variables between the two groups were analysed for statistical significance. Eighty seven out of one hundred and thirty subjects have completed the study (VD:44, NVD:43). Vitamin D level has increased from 16 ± 6 ng/ml to 89 ± 32 ng/ml after Pulse D therapy in VD group and highly significant (p < 0.01) reduction of all the measured inflammatory markers was noted. Reduction of markers in NVD group was insignificant (p > 0.05). The difference in the reduction of markers between the groups (NVD vs VD) was highly significant (p < 0.01). Therapeutic improvement in vitamin D to 80-100 ng/ml has significantly reduced the inflammatory markers associated with COVID-19 without any side effects. Hence, adjunctive Pulse D therapy can be added safely to the existing treatment protocols of COVID-19 for improved outcomes.