Vitamin D binding protein and its polymorphisms may explain the link between vitamin D deficiency and COVID-19.
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ABSTRACT:
SUBMITTER: Speeckaert MM
PROVIDER: S-EPMC10306132 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Vitamin D binding protein and its polymorphisms may explain the link between vitamin D deficiency and COVID-19.
Speeckaert Marijn M MM Delanghe Joris R JR
Science progress 20211001 4
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| S-EPMC7861048 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) pandemic has been the subject of a large number of studies in recent times. Here, starting from the evidence that in Italy, the areas with the lowest number of COVID-19 cases were those with the highest incidence of malaria in the early 1900's, we explore possible inverse relationships between malaria and COVID-19. Indeed, some genetic variants, which have been demonstrated to give an advantage against malaria, can also play a role in the incidence and severity of SARS-CoV-2 infections (e.g., the ACE2 receptor). To verify this scientific hypothesis, we here use public data from whole-genome sequencing (WGS) experiments to extrapolate the genetic information of 46 world populations with matched COVID-19 data. In particular, we focus on 47 genes, including ACE2 and genes which have previously been reported to play a role in malaria. Only common variants (>5%) in at least 30% of the selected populations were considered, and, for this subset, we correlate the intra-population allele frequency with the COVID-19 data (cases/million inhabitants), eventually pinpointing meaningful variants in 6 genes. This study allows us to distinguish between positive and negative correlations, i.e., variants whose frequency significantly increases with increasing or decreasing COVID-19 cases. Finally, we discuss the possible molecular mechanisms associated with these variants and advance potential therapeutic options, which may help fight and/or prevent COVID-19.
| S-EPMC8107224 | biostudies-literature
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| S-EPMC8017947 | biostudies-literature
Project description:Coronavirus Disease 2019 (COVID-19) pandemic remains a major public health threat in most countries. The causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can lead to acute respiratory distress syndrome and result in mortality in COVID-19 patients. Vitamin D is an immunomodulator hormone with established effectiveness against various upper respiratory infections. Vitamin D can stall hyper-inflammatory responses and expedite healing process of the affected areas, primarily in the lung tissue. Thus, there are ecological and mechanistic reasons to promote exploration of vitamin D action in COVID-19 patients. As no curative drugs are available currently for COVID-19, we feel that the potential of vitamin D to alter the course of disease severity needs to be investigated. Clinical studies may be undertaken to address the value of vitamin D supplementation in deficient, high-risk COVID-19 patients.
| S-EPMC7500624 | biostudies-literature
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| S-EPMC8129783 | biostudies-literature
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| S-EPMC8038533 | biostudies-literature
Project description:BackgroundVitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D-binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound ("free") and albumin-bound ("bioavailable") 25(OH)D have been proposed.ObjectivesWe aimed to examine the relationship between vitamin D status and mortality from COVID-19.MethodsIn this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression.ResultsThere were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34-98 years) than survivors (mean age, 65 years; range, 19-95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17-4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51-14.34) compared with a 25(OH)D value of 50-74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality.ConclusionsVitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).
| S-EPMC8903333 | biostudies-literature
Project description:BackgroundDisease 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.MethodsWe 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.ResultsWe 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.ConclusionWhile 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.
| S-EPMC7989070 | biostudies-literature
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| S-EPMC7882234 | biostudies-literature
Project description:It's since December 2019 that Corona virus disease (COVID-19) has emerged to be the global issue of concern. A "pandemic"; this is what WHO has declared about the COVID-19 outbreak on March 3rd, 2020. Vitamin D and its deficiency have recently been claimed to be one of the potential factors affecting COVID-19 risks and outcomes [1]. As Selberstein et al., has recently discussed the effect of vitamin D deficiency, and the role of vitamin D supplementation in COVID-19 patients [2], I'd believe that vitamin D binding protein (DBP) is maybe also involved. A closer look on DBP and its action on regulating the circulatory vitamin D levels, its polymorphisms and their impact on COVID-19 prevalence and mortality, will be briefly discussed.
| S-EPMC7871104 | biostudies-literature