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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.
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Vitamin D insufficiency as a potential culprit in critical COVID-19 patients.
Munshi, R, Hussein, MH, Toraih, EA, Elshazli, RM, Jardak, C, Sultana, N, Youssef, MR, Omar, M, Attia, AS, Fawzy, MS, et al
Journal of medical virology. 2021;(2):733-740
Abstract
BACKGROUND As an immune modulator, vitamin D has been implicated in the coronavirus disease-2019 (COVID-19) outcome. We aim to systematically explore the association of vitamin D serum levels with COVID-19 severity and prognosis. METHODS The standardized mean difference (SMD) or odds ratio and 95% confidence interval (CI) were applied to estimate pooled results from six studies. The prognostic performance of vitamin D serum levels for predicting adverse outcomes with detection of the best cutoff threshold was determined by receiver operating characteristic curve analysis. Decision tree analysis by combining vitamin D levels and clinical features was applied to predict severity in COVID-19 patients. RESULTS Mean vitamin D serum level of 376 patients, was 21.9 nmol/L (95% CI = 15.36-28.45). Significant heterogeneity was found (I2 = 99.1%, p < .001). Patients with poor prognosis (N = 150) had significantly lower serum levels of vitamin D compared with those with good prognosis (N = 161), representing an adjusted standardized mean difference of -0.58 (95% Cl = -0.83 to -0.34, p < .001). CONCLUSION Serum vitamin D levels could be implicated in the COVID-19 prognosis. Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients' potential of developing severe COVID-19. Appropriate preventative and/or therapeutic intervention may improve COVID-19 outcomes.
3.
"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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Abstract
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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Vitamin D supplementation, COVID-19 and disease severity: a meta-analysis.
Shah, K, Saxena, D, Mavalankar, D
QJM : monthly journal of the Association of Physicians. 2021;(3):175-181
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OBJECTIVE Current meta-analysis aims to understand the effect of oral supplementation of vitamin D on intensive care unit (ICU) requirement and mortality in hospitalized COVID-19 patients. METHODS Databases PubMed, preprint servers, and google scholar were searched from December 2019 to December 2020. Authors searched for the articles assessing role of vitamin D supplementation on COVID-19. Cochrane RevMan tool was used for quantitative assessment of the data, where heterogeneity was assessed using I2 and Q statistics and data was expressed using odds ratio with 95% confidence interval. RESULTS Final meta-analysis involved pooled data of 532 hospitalized patients (189 on vitamin D supplementation and 343 on usual care/placebo) of COVID-19 from three studies (Two randomized controlled trials, one retrospective case-control study). Statistically (p<0.0001) lower ICU requirement was observed in patients with vitamin D supplementation as compared to patients without supplementations (odds ratio: 0.36; 95% CI: 0.210-0.626). However, it suffered from significant heterogeneity, which reduced after sensitivity analysis. In case of mortality, vitamin D supplements has comparable findings with placebo treatment/usual care (odds ratio: 0.93; 95% CI: 0.413-2.113; p=0.87). The studies did not show any publication bias and had fair quality score. Subgroup analysis could not be performed due to limited number of studies and hence dose and duration dependent effect of vitamin D could not be evaluated. CONCLUSIONS Although the current meta-analysis findings indicate potential role of vitamin D in improving COVID-19 severity in hospitalized patients, more robust data from randomized controlled trials are needed to substantiate its effects on mortality.