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1.
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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2.
[Vitamin D supplementation and COVID-19: expert consensus and guidelines].
Annweiler, C, Souberbielle, JC
Geriatrie et psychologie neuropsychiatrie du vieillissement. 2021;(1):20-29
Abstract
After 12 months of viral circulation, the SARS-CoV-2 has infected millions of people around the world, leaving hundreds of thousands dead. With the lack of effective therapy and vaccination against COVID-19, focusing on the immediate repurposing of existing drugs gives hope of curbing the pandemic. Vitamin D is a possible candidate discussed in a high amount of publications. Randomized clinical trials show that vitamin D supplementation significantly reduces the risk of respiratory infections. There are also many evidences that hypovitaminosis D is an independent (and easily modifiable) risk factor for severe forms of COVID-19 and death. Vitamin D supplementation is a simple, safe and inexpensive measure, which is effective in correcting hypovitaminosis D found in 40-50% of the French population and in more than 80% of adults with COVID-19. In this position paper, we propose simple regimens (adapted to the pharmaceutical forms currently available in France) for vitamin D supplementation in adults with or without COVID-19.
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Potential immunomodulatory effects of vitamin D in the prevention of severe coronavirus disease 2019: An ally for Latin America (Review).
Turrubiates-Hernández, FJ, Sánchez-Zuno, GA, González-Estevez, G, Hernández-Bello, J, Macedo-Ojeda, G, Muñoz-Valle, JF
International journal of molecular medicine. 2021;(4)
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Abstract
Currently, the world is under a pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), responsible for coronavirus disease 2019 (COVID‑19). This disease is characterized by a respiratory syndrome that can progress to an acute respiratory distress syndrome. To date, limited effective therapies are available for the prevention or treatment of COVID‑19; therefore, it is necessary to propose novel treatment options with immunomodulatory effects. Vitamin D serves functions in bone health and has been recently reported to exert protective effects against respiratory infections. Observational studies have demonstrated an association between vitamin D deficiency and a poor prognosis of COVID‑19; this is alarming as vitamin D deficiency is a global health problem. In Latin America, the prevalence of vitamin D deficiency is unknown, and currently, this region is in the top 10 according to the number of confirmed COVID‑19 cases. Supplementation with vitamin D may be a useful adjunctive treatment for the prevention of COVID‑19 complications. The present review provides an overview of the current knowledge of the potential immunomodulatory effects of vitamin D in the prevention of COVID‑19 and sets out vitamin D recommendations for the Latin American population.
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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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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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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 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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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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"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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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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Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.
Jolliffe, DA, Camargo, CA, Sluyter, JD, Aglipay, M, Aloia, JF, Ganmaa, D, Bergman, P, Bischoff-Ferrari, HA, Borzutzky, A, Damsgaard, CT, et al
The lancet. Diabetes & endocrinology. 2021;(5):276-292
Abstract
BACKGROUND A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING None.