Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause and consequence

Smolders, Joost; Ouweland, Jody van den; Geven, Christopher; Pickkers, Peter; Kox, Matthijs

doi:10.1016/j.metabol.2020.154434

Cited by 73 publications

(72 citation statements)

References 6 publications

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“…In fact, 25(OH)D levels may decrease by 40% within the first 24 h of acute illness [ 86 , 87 ]. Injection of E.coli lipopolysaccharides induced inflammation in normal volunteers and resulted in an acute decrease in mean serum 25(OH)D levels by 2.6 ng/ml, as measured by mass spectroscopy, 2–3 h later [ 90 , 91 ]. Furthermore, decreased synthesis of vitamin D binding proteins and increased 25(OH)D renal excretion, may play a significant role in regulating vitamin D levels in critically ill patients [ 88 , 89 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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/d, 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/d, 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Among patients with COVID-19, the disease resulting from SARS-CoV-2 infection followed by a dysregulated immune response, low levels of 25(OH)D at time of diagnosis have been associated with more severe illness [ 136 , 137 , 138 ]. Reverse causation cannot be excluded because serum 25(OH)D level decreases in response to acute inflammatory disease [ 139 , 140 ], but serum 25(OH)D levels have been associated with SARS-CoV-2 virus positivity using seasonally-adjusted 25(OH)D levels from the preceding 12 months [ 141 , 142 ].…”

Section: Current Status Of Knowledgementioning

confidence: 99%

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

2021

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African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer’s disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.

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“…Second, the association between vitamin D status at the time of hospitalization and outcomes of acute inflammatory illness is likely due in part to reverse causation. Low level of serum 25(OH)D could also be secondary to systemic inflammatory response which results in vascular leakage of vitamin D-binding protein and albumin as well as increased catabolism of 25(OH)D ( 105 , 106 ). Third, vitamin D might benefit each individual differently as significant inter-individual difference in responsiveness to vitamin D supplement has been reported ( 33 , 34 , 35 ).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D and Its Potential Benefit for the COVID-19 Pandemic

2021

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Vitamin D is known not only for its importance for bone health, but also for its biologic activities on other many other organ systems. This is due to the presence of the vitamin D receptor (VDR) in various types of cells and tissues, including the skin, skeletal muscle, adipose tissue, endocrine pancreas, immune cells and blood vessels. Experimental studies have shown that vitamin D exerts several actions that are thought to be protective against COVID-19 infectivity and severity. These include the immunomodulatory effects on the innate and adaptive immune systems, the regulatory effects on renin-angiotensin-aldosterone-system in the kidneys and the lungs, and the protective effects against endothelial dysfunction and thrombosis. Prior to the COVID-19 pandemic, studies have shown that vitamin D supplementation is beneficial in protecting against risk of acquiring acute respiratory viral infection and may improve outcomes in sepsis and critically ill patients. There are a growing number of data connecting COVID-19 infectivity and severity with vitamin D status, suggesting a potential benefit of vitamin D supplementation for primary prevention or as an adjunctive treatment of COVID-19. Although the results from most ongoing randomized clinical trials aiming to prove the benefit of vitamin D supplementation for these purposes are still pending, there is no downside to increasing vitamin D intake and having sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at least 30 ng/mL (75 nmol/L) and preferably at 40 – 60 ng/mL (100 – 150 nmol/L) to minimize the risk of COVID-19 infection and its severity.

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Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause and consequence

Cited by 73 publications

References 6 publications

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

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

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

Vitamin D and Its Potential Benefit for the COVID-19 Pandemic

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