Abstract
Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections. Most of the clinical studies of vitamin D in COVID-19 have been observational, and the most serious problem with observational study design is that of confounding. Observational studies typically assess the relationship of 25(OH)D values with COVID-19 outcomes. Many conditions associated with low vitamin D status are also associated with worse COVID-19 outcomes. Randomized controlled trials (RCTs) overcome the problem of confounding, typically comparing outcomes between groups receiving vitamin D supplementation or placebo. However, any benefit of vitamin D in COVID-19 may be related to the dose, duration, daily vs. bolus administration, interaction with other treatments, and timing of administration prior to or during the illness. Serum 25(OH)D values >50 nmol/L have been associated with reduced infection rates, severity of COVID-19, and mortality in observational studies. Few RCTs of vitamin D supplementation have been completed, and they have shown no benefit of vitamin D in hospitalized patients. Vitamin D may benefit those with mild or asymptomatic COVID-19, and those with greater 25(OH)D values may have lower risk of acquiring infection. Because those at greatest risk of COVID-19 are also at greatest risk of vitamin D deficiency, it is reasonable to recommend vitamin D supplementation 15–20 mcg (600–800 IU) daily for the general population during the COVID-19 pandemic. Vitamin D doses greater than 100 mcg (4000 IU) daily should not be used without monitoring serum 25(OH)D and calcium.
Highlights
Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections
The GRADE scoring methodology can be used as a means of formally evaluating study quality and making recommendations [5], and the focus of this review is to enable the reader to understand the limitations of study design and appropriately assess study quality
All increase the risk of adverse outcomes from COVID-19, but most of these conditions have been associated with lower vitamin D status, as measured by serum 25(OH)D
Summary
Vitamin D deficiency has classically been associated with the bone diseases of rickets in growing children and osteomalacia in adults [1]. Increasing interest in the non-skeletal effects of vitamin D relates to the finding of vitamin D receptors (VDR) widely distributed in most human tissues, as is the 1α-hydroxylase enzyme (CYP27B1). Alveolar macrophages, and dendritic cells involved in cytokine production All these cells express 1a-hydroxylase and are capable of locally producing 1,25(OH) D, which acts as an important immune and inflammatory modulator. Vitamin D could have benefit in COVID-19 in three different ways: (1) reducing the risk of acquiring SARS-CoV-2 infection, (2) enhancing viral neutralization and clearance, and (3) reducing the severity of the inflammatory response [2]. Laboratory evidence demonstrates that 1,25(OH) D promotes the expression of antimicrobial proteins cathelicidin and β-defensin by pulmonary macrophages and epithelium It suppresses antigen presentation by dendritic cells and activation of T cells, thereby inhibiting proinflammatory cytokine production.
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