A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency

Abstract

As the world's attention has been riveted upon the growing COVID-19 pandemic, many researchers have written brief reports supporting the hypothesis that vitamin D deficiency is related to the incidence and severity of COVID-19. The clear common thread among the top risk groups-vitamin D deficiency-may be being overlooked because of previous overstated claims of vitamin D benefits. However, the need to decrease COVID-19 fatalities among high-risk populations is urgent. Early researchers reported three striking patterns. Firstly, the innate immune system is impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency also increases the activity of the X-chromosome-linked "Renin-Angiotensin" System, making vitamin D deficient individuals (especially men) more susceptible to COVID-19's deadly "cytokine storm" (dramatic immune system overreaction). Secondly, the groups who are at highest risk for severe COVID-19 match those who are at highest risk for severe vitamin D deficiency. This includes the elderly, men, ethnic groups whose skin is naturally rich in melanin (if living outside the tropics), those who avoid sun exposure for cultural and health reasons, those who live in institutions, the obese, and/or those who suffer with hypertension, cardiovascular disease, or diabetes. And thirdly, the pattern of geographical spread of COVID-19 reflects higher population vitamin D deficiency. Both within the USA and throughout the world, COVID-19 fatality rates parallel vitamin D deficiency rates. A literature search was performed on PubMed, Google Scholar, and RSMLDS, with targeted Google searches providing additional sources. Although randomized controlled trial results may be available eventually, the correlational and causal study evidence supporting a link between vitamin D deficiency and COVID-19 risks is already so strong that it supports action. The 141 author groups writing primarily about biological plausibility detailed how vitamin D deficiency can explain every risk factor and every complication of COVID-19, but agreed that other factors are undoubtedly at work. COVID-19 was compared with dengue fever, for which oral vitamin D supplements of 4,000 IU for 10 days were significantly more effective than 1,000 IU in reducing virus replication and controlling the "cytokine storm" (dramatic immune system over-reaction) responsible for fatalities. Among the 47 original research studies summarized here, chart reviews found that serum vitamin D levels predicted COVID-19 mortality Benskin Evidence Linking Vitamin D, COVID-19 rates (16 studies) and linearly predicted COVID-19 illness severity (8 studies). Two causal modeling studies and several analyses of variance strongly supported the hypothesis that vitamin D deficiency is a causal, rather than a bystander, factor in COVID-19 outcomes. Three of the four studies whose findings opposed the hypothesis relied upon disproven assumptions. The literature review also found that prophylactically correcting possible ...

Sex-specific association between vitamin D deficiency and COVID-19 mortality in older patients

“…In the research efforts to identify drivers/risk factors for COVID-19 mortality, the role of vitamin D has received attracted interest, especially given its potent modulatory action on the immune system and on the renin-angiotensin system (RAS), particularly the angiotensin-converting enzyme2 (ACE2), the main host cell receptor of SARS-CoV-2 [3,4]. However, studies failed to explicitly address the effect of sex on the associations between vitamin D and COVID-19 outcomes.…”

“…Especially they should inform the design and interpretation of awaited interventional trials evaluating the therapeutic potential of vitamin D supplementation in older COVID-19 patients. The mechanisms behind the sex-differential association, such as the implication of vitamin D deficiency on the X-chromosome linked RAS activity, remain to be fully elucidated [4].…”

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update

“…Below we provide more details of possible protective mechanisms of action of vitamin D, review new findings around the associations between blood 25(OH)D and COVID-19, and discuss issues around vitamin D supplementation and clinical trials in this space. Readers are also directed toward a review (162) of the many commentaries already published in the vitamin D and COVID-19 space, which also provides comprehensive details of earlier studies published until the 16th June 2020, as well as another comprehensive review of studies published until 27th September 2020 (161). infection.…”

Vitamin D and SARS-CoV-2 infection—evolution of evidence supporting clinical practice and policy development

“…Previous research has shown that in Ireland, total vitamin D 3 intake of~25-30 μg/day (1000-1200 IU/day) is required to reliably maintain 25(OH)D > 50 nmol/l on a year-round basis in adults aged 20-40 years [68], and in those aged 64 years and over [69]. However, it has been more recently argued in the USA that intakes of 37.5-50 μg/day (1500-2000 IU/day) are required for specific protection against SARS-CoV-2 infection and Covid-19 illness [30,70]. Given our high national prevalence of obesity, it is possible that these higher requirements for protection against Covid-19 may also pertain amongst some vulnerable population groups in Ireland, as the dosage needed to achieve the same increment in serum 25(OH)D concentration is thought to rise by~40% in obesity [71].…”