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The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis.

ABSTRACT:

Background

Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D deficiency. Vitamin D plays an important role in immune function and inflammation. This systematic review and meta-analysis assesses the impact of vitamin D status and supplementation on COVID-19 related mortality and health outcomes.

Methods

We searched four databases until December 18th 2020, and trial registries until January 20th 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and graded the evidence for each outcome across studies, independently and in duplicate. Pre-specified outcomes of interest were mortality, ICU admission, invasive and non-invasive ventilation, hospitalization, time of hospital stay, disease severity and SARS-CoV-2 positivity. We only included data from peer-reviewed articles in our primary analyses.

Results

We identified 31 peer-reviewed observational studies. In our primary analysis, there was a positive trend between serum 25(OH)D level <20 ng/ml and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. However, these associations were not statistically significant. Mean 25(OH)D levels was 5.9 ng/ml (95% CI [-9.5, -2.3]) significantly lower in COVID-19 positive, compared to negative patients. The certainty of the evidence was very low. We identified 32 clinical trial protocols, but only three have published results to-date. The trials administer vitamin D doses of 357 to 60,000 IU/day, from one week to 12 months. Eight megatrials investigate the efficacy of vitamin D in outpatient populations. A pilot trial revealed a significant decrease in ICU admission with calcifediol, compared to placebo (OR = 0.003), but the certainty of the evidence was unclear. Another small trial showed that supplementation with cholecalciferol, 60,000 IU/day, decreased fibrinogen levels, but did not have an effect on D-dimer, procalcitonin and CRP levels, compared to placebo. The third trial did not find any effect of vitamin D supplementation on COVID-19 related health outcomes.

Conclusion

While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.

SUBMITTER: Bassatne A

PROVIDER: S-EPMC7989070 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2), millions of people have died, and the medical system has faced significant difficulties. Our purpose was to perform a meta-analysis to estimate the effect of vitamin C on in-hospital mortality and the ICU or hospital length of stay for patients diagnosed with COVID-19. We conducted a systematic review with meta-analysis in the following databases: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials. We included studies that evaluated the effect of vitamin C supplementation, compared with standard treatment in COVID-19 patients who are ≥18 y of age. Nineteen trials were included in the meta-analysis. In-hospital mortality with and without vitamin C supplementation was 24.1% vs. 33.9% (OR = 0.59; 95%CI: 0.37 to 0.95; p = 0.03), respectively. Sub-analysis showed that, in randomized clinical trials, in-hospital mortality varied and amounted to 23.9% vs. 35.8% (OR = 0.44; 95%CI: 0.25 to 0.76; p = 0.003), respectively. In the non-randomized trials, in-hospital mortality was 24.2% vs. 33.5% (OR = 0.72; 95%CI: 0.38 to 1.39; p = 0.33), respectively. The ICU length of stay was longer in patients treated with vitamin C vs. standard therapy, 11.1 (7.3) vs. 8.3 (4.7) days (MD = 1.91; 95%CI: 0.89 to 2.93; p < 0.001), respectively. Acute kidney injury in patients treated with and without vitamin C varied and amounted to 27.8% vs. 45.0% (OR = 0.56; 95%CI: 0.40 to 0.78; p < 0.001), respectively. There were no differences in the frequency of other adverse events among patients' treatment with and without vitamin C (all p > 0.05). The use of vitamin C reduces hospital mortality. The length of stay in the ICU is longer among patients treated with vitamin C. In terms of patient safety, vitamin C has an acceptable profile. Low doses of vitamin C are effective and safe. Despite some evidence of the usefulness of vitamin C in modifying the course of COVID-19, it is too early to modify guidelines and recommendations. Further studies, in particular randomized clinical trials, are necessary.

Project description:Objective To systematically evaluate the impact of vitamin D supplementation on mortality, ICU admission, and the rates of mechanical ventilation or intubation among COVID-19 patients. Data sources and study selection The PubMed, Embase, Cochrane Library, CBM, CNKI, VIP, and WanFang databases were searched from 1 December 2019 to 31 December 2022. The authors sought to identify randomized controlled trials and cohort studies that examined the relationship between vitamin D supplementation and mortality, ICU admission, and mechanical ventilation or intubation rates among COVID-19 patients. Data extraction and synthesis Two investigators independently searched the literature, extracted the data, and assessed the quality of the included studies. The Grading of Recommendation, Assessment, Development, and Evaluation approach was used to evaluate the quality of the evidence. Meta-analysis was conducted using RevMan 5.3, STATA 15.1, and R 4.1.3 software. Results Eight randomized controlled trials (RCTs) and eight cohort studies were included, involving 3359 COVID-19 patients. The pooled analysis of randomized controlled trials showed that vitamin D supplementation did not have a significant effect on reducing mortality (Relative Risk, RR = 0.94, 95% CI 0.69–1.29, P = 0.7), while the results of cohort studies indicated that vitamin D supplementation had a positive impact on reducing mortality among COVID-19 patients (RR = 0.33, 95% CI 0.23–0.47, P < 0.001). There was no statistically significant difference in the rates of ICU admission (RCTs: RR = 0.64, 95%CI 0.38–1.08, P = 0.10; cohort studies: RR = 0.32, 95% CI 0.08–1.29, P = 0.109) or rates of mechanical ventilation or intubation (RCTs: RR = 0.77, 95% CI 0.58–1.02, P = 0.07; cohort studies: RR = 0.93, 95% CI 0.55–1.58, P = 0.789). Conclusion The results of this systematic review and meta-analysis suggest that vitamin D supplementation does not have a significant impact on reducing mortality, ICU admission, and the rates of mechanical ventilation or intubation among COVID-19 patients. However, due to the limited number and quality of the studies included, further high-quality studies are needed to confirm these findings. Systematic review registration www.crd.york.ac.uk, identifier CRD42021299521.