Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis.
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ABSTRACT: Background
We sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID-19) infection.Methods
Multiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID-19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission.Results
Seventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50-4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40-7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48-3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25-0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut-offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends.Conclusions
Vitamin D deficiency is associated with greater severity of COVID-19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID-19.
SUBMITTER: Wang Z
PROVIDER: S-EPMC8444883 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This systematic review was conducted to summarize and clarify the evidence on the association between 25-hydroxyvitamin-D [25(OH)D] concentrations and coronavirus disease 2019 (COVID-19) risk and outcomes. PubMed, Scopus, and Web of Science databases and Google Scholar were searched up to 26 November 2020. All retrospective and prospective cohort, cross-sectional, case-control, and randomized controlled trial studies that investigated the relation between 25(OH)D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity were included. Thirty-nine studies were included in the current systematic review. In studies that were adjusted (OR: 1.77; 95% CI: 1.24, 2.53; I2: 44.2%) and nonadjusted for confounders (OR: 1.75; 95% CI: 1.44, 2.13; I2: 33.0%) there was a higher risk of SARS-CoV-2 infection in the vitamin D deficiency (VDD) group. Fifteen studies evaluated associations between VDD and composite severity. In the studies that were adjusted (OR: 2.57; 95% CI: 1.65, 4.01; I2 = 0.0%) and nonadjusted for confounders (OR: 10.61; 95% CI: 2.07, 54.23; I2 = 90.8%) there was a higher severity in the VDD group. Analysis of studies with crude OR (OR: 2.62; 95% CI: 1.13, 6.05; I2: 47.9%), and adjusted studies that used the Cox survival method (HR: 7.67; 95% CI: 3.92, 15.03; I2: 0.0%) indicated a significant association of VDD with mortality, while in adjusted studies that used logistic regression, no relation was observed (OR: 1.05; 95% CI: 0.63, 1.75; I2: 76.6%). The results of studies that examined relations between VDD and intensive care unit (ICU) admission, pulmonary complications, hospitalization, and inflammation were inconsistent. In conclusion, although studies were heterogeneous in methodological and statistical approach, most of them indicated a significant relation between 25(OH)D and SARS-CoV-2 infection, COVID-19 composite severity, and mortality. With regard to infection, caution should be taken in interpreting the results, due to inherent study limitations. For ICU admission, inflammation, hospitalization, and pulmonary involvement, the evidence is currently inconsistent and insufficient.
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Project description:ObjectivesExtensive evidence links low vitamin D status and comorbidities with coronavirus disease 2019 (COVID-19) outcomes, but the results of published studies are contradictory. Therefore, we investigated the association of lower levels of vitamin D and comorbidities with the risk of COVID-19 infection.MethodsWe searched MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for articles published until August 20, 2021. Sixteen eligible studies were identified (386 631 patients, of whom 181 114 were male). We included observational cohort and case-control studies that evaluated serum levels of vitamin D in COVID-19-positive and COVID-19-negative patients. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated.ResultsSignificantly lower vitamin D levels were found in COVID-19-positive patients (MD, -1.70; 95% CI, -2.74 to -0.66; p=0.001), but with variation by study design (case-control: -4.04; 95% CI, -5.98 to -2.10; p<0.001; cohort: -0.39; 95% CI, -1.62 to 0.84; p=0.538). This relationship was more prominent in female patients (MD, -2.18; 95% CI, -4.08 to -0.28; p=0.024) than in male patients (MD, -1.74; 95% CI, -3.79 to 0.31; p=0.096). Male patients showed higher odds of having low vitamin D levels (odds ratio [OR], 2.09; 95% CI, 1.38 to 3.17; p<0.001) than female patients (OR, 1.17; 95% CI, 0.74 to 1.86; p=0.477). Comorbidities showed inconsistent, but generally non-significant, associations with COVID-19 infection.ConclusionsLow serum vitamin-D levels were significantly associated with the risk of COVID-19 infection. This relationship was stronger in female than in male COVID-19 patients. Limited evidence was found for the relationships between comorbidities and COVID-19 infection, warranting large population-based studies to clarify these associations.
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Project description:BackgroundThe evidence regarding the efficacy of vitamin D supplementation in reducing severity of COVID-19 is still insufficient. This is partially due to the lack of primary robust trial-based data and heterogeneous study designs.AimThis evidence summary, aims to study the effect of vitamin D supplementation on morbidity and mortality in hospitalized COVID-19 patients.Design: Evidence summary of systematic reviews.MethodsFor this study, systematic reviews and meta-analysis published from December 2019 to January 2022 presenting the impact of vitamin D supplementation on COVID-19 severity were screened and selected from PubMed and Google scholar. After initial screening, 10 eligible reviews were identified and quality of included reviews were assessed using AMSTAR and GRADE tools and overlapping among the primary studies used were also assessed.ResultsThe number of primary studies included in the systematic reviews ranged from 3 to 13. Meta-analysis of seven systematic reviews showed strong evidence that vitamin D supplementation reduces the risk of mortality (Odds ratio: 0.48, 95% CI: 0.346-0.664; P < 0.001) in COVID patients. It was also observed that supplementation reduces the need for intensive care (Odds ratio: 0.35; 95%CI: 0.28-0.44; P < 0.001) and mechanical ventilation (Odds ratio: 0.54; 95% CI: 0.411-0.708; P < 0.001) requirement. The findings were robust and reliable as level of heterogeneity was considerably low. However the included studies were of varied quality. Qualitative analysis showed that supplements (oral and IV) are well tolerated, safe and effective in COVID patients.ConclusionThe findings of this study show that vitamin D supplementation is effective in reducing the COVID-19 severity. Hence, vitamin D should be recommended as an adjuvant therapy for COVID-19.However, more robust and larger trials are required to substantiate it further.
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Project description:We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation. Vitamin D deficiency and insufficiency were associated with increased severity and unfavourable outcome after 28 days. Vitamin D levels were negatively associated with biomarkers of COVID-19 severity. Vitamin D supplementation after challenge of mice with COVID-19 plasma led to reduced levels of TNFα, IL-6, IFNγ and MPO in the lung, as well as down-regulation of pro-inflammatory pathways as derived from RNA-seq experiments. Thus, vitamin D demonstrates a protective effect against severity and unfavorable outcome in COVID-19, possibly through attenuation of tissue-specific hyperinflammation.
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Project description:Vitamin D is associated with biological activities of the innate and adaptive immune systems, as well as inflammation. In observational studies, an inverse relationship has been found between serum 25-hydroxyvitamin D (25(OH)D) concentrations and the risk or severity of coronavirus disease 2019 (COVID-19). Several mechanisms have been proposed for the role of vitamin D in COVID-19, including modulation of immune and inflammatory responses, regulation of the renin-angiotensin-aldosterone system, and involvement in glucose metabolism and cardiovascular system. Low 25(OH)D concentrations might predispose patients with COVID-19 to severe outcomes not only via the associated hyperinflammatory syndrome but also by worsening preexisting impaired glucose metabolism and cardiovascular diseases. Some randomized controlled trials have shown that vitamin D supplementation is beneficial for reducing severe acute respiratory syndrome coronavirus 2 RNA positivity but not for reducing intensive care unit admission or all-cause mortality in patients with moderate-to-severe COVID-19. Current evidence suggests that taking a vitamin D supplement to maintain a serum concentration of 25(OH)D of at least 30 ng/mL (preferred range 40-60 ng/mL), can help reduce the risk of COVID-19 and its severe outcomes, including mortality. Although further well designed studies are warranted, it is prudent to recommend vitamin D supplements to people with vitamin D deficiency/insufficiency during the COVID-19 pandemic according to international guidelines.
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Project description:BackgroundAn increasing number of scientific journals have proposed a connection between tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the severity of COVID-19. Vitamin D has been discussed as a potential therapy for COVID-19 due to its immunomodulatory effects. This meta-analysis aims to determine the relationship, if any, between TNF-α, IL-6, vitamin D, and COVID-19 severity and mortality.MethodsThe design of the study is a systematic review and meta-analysis. A literature search is performed using PubMed, Cochrane, ProQuest, and Google Scholar.ResultsTNF-α insignificantly increases the risk of COVID-19 severity (adjusted odds ratio (aOR) = 1.0304; 95% CI 0.8178-1.2983; p = 0.80) but significantly increases the risk of COVID-19 mortality (crude hazard ratio (HR) = 1.0640; 95% CI 1.0259-1.1036; p = 0.0009). IL-6 significantly increases the risk of COVID-19 severity (aOR = 1.0284; 95% CI 1.0130-1.0441; p = 0.0003) and mortality (aOR = 1.0076; 95% CI 1.0004-1.0148; p = 0.04; adjusted hazard ratio (aHR) = 1.0036; 95% CI 1.0010-1.0061; p = 0.006). There is a statistically insignificant difference of the mean vitamin D levels between patients with severe COVID-19 and non-severe COVID-19 (mean difference (MD) = -5.0232; 95% CI 11.6832-1.6368; p = 0.14). A vitamin D deficiency insignificantly increases the risk of mortality of COVID-19 patients (aOR = 1.3827; 95% CI 0.7103-2.6916; p = 0.34).ConclusionIL-6 is an independent prognostic factor towards COVID-19 severity and mortality.
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