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 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 vitamin D deficiency during the COVID-19 pandemic is extremely safe. Widely recommending 2,000 IU of vitamin D daily for all populations with limited ability to manufacture vitamin D from the sun has virtually no potential for harm and is reasonably likely to save many lives.

Keywords: COVID-19; health disparities; minority health; preventive medicine; vitamin D; vitamin D deficiency.

Graphical Abstract

Search and reporting method.

Figure 1

Study authors' supplementation support by country.

Figure 2

(A) Interest in the topic—Biological plausibility article authors' locations (141 Articles). (Blank maps from wiki images: Creative Commons, credit: Canuckguy and many others). (B) Interest in the topic – Original research article authors' locations (47 Articles). (Blank map from wiki images: Creative Commons, credit: Canuckguy and many others).

Figure 3

Davies et al., Causal model results (63).

Figure 4

Some of the results of the retrospective chart review by Alipio et al. (3). Of the 212 hospitalized COVID-19 patients, 96% of those with mild COVID-19 had normal vitamin D levels (above 30 ng/ml). In contrast, over 50% of the patients with severe or critical COVID-19 were vitamin D deficient (level 20 ng/ml or lower).

Figure 5

Some of the results of the retrospective chart review by D'Avolio et al. (124). In the 107 individuals tested for both 25(OH)D and COVID-19, vitamin D predicted infection.

Figure 6

Some of the results of the retrospective chart review by Lau et al. (157). In the 20 hospitalized individuals tested for both 25(OH)D and COVID-19, vitamin D predicted severity of infection.

Figure 7

Some of the results of the retrospective chart review by Glicio et al. (5). In the 176 elderly (over age 60) hospitalized individuals tested for both 25(OH)D and COVID-19, vitamin D predicted severity of infection.

Figure 8

Word Cloud of recommendations from authors of 47 studies.