The Role of Vitamin D in the Age of COVID-19: A Systematic Review and Meta-Analysis

Abstract

Background: Following emerge of a novel coronavirus from Wuhan, China, in December 2019, it has affected the whole world and after months of efforts by the medical communities, there is still no specific approach for prevention and treatment against the Coronavirus Disease 2019 (COVID-19). Evidence recommends that vitamin D might be an important supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a rapid systematic review and meta-analysis along with an ecological investigation in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as preprint database of medRxiv, bioRxiv, Research Square, preprints.org, search engine of ScienceDirect and a rapid search through famous journals up to May 26, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Along with our main aim, to find the second objective: correlation of global vitamin D status and COVID-19 recovery and mortality we carried out a literature search in PubMed database to identify the national or regional studies reported the vitamin D status globally. CMA v. 2.2.064 and SPSS v.16 were used for data analysis. Results: Out of nine studies entered into our systematic review, six studies containing 3,822 participants entered into the meta-analysis. The meta-analysis indicated that 46.5% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 28.2%-65.8%) and in 43.3% of patients, levels of vitamin D were insufficient (95% CI, 27.4%-60.8%). In regard to our ecological investigation on 51 countries including 408,748 participants, analyses indicated no correlation between vitamin D levels and recovery rate (r= 0.041) as well as mortality rate (r=−0.073) globally. However, given latitude, a small reverse correlation between mortality rate and vitamin D status was observed throughout the globe (r= −0.177). In Asia, a medium direct correlation was observed for recovery rate (r= 0.317) and a significant reveres correlation for mortality rate (r= −0.700) with vitamin D status in such patients. In Europe, there were no correlations for both recovery (r= 0.040) and mortality rate (r= −0.035). In Middle East, the recovery rate (r= 0.267) and mortality rate (r= −0.217) showed a medium correlation. In North and Sought America, surprisingly, both recovery and mortality rate demonstrated a direct correlation respectively (r= 1.000, r=0.500). In Oceania, unexpectedly, recovery (r= −1.000) and mortality (r= −1.000) rates were in considerable reverse correlation with vitamin D levels. Conclusion: In this systematic review and meta-analysis with an ecological approach, we found a high percentage of COVID-19 patients who suffer from vitamin D deficiency or insufficiency. Much more important, our ecological investigation resulted in substantial direct and reverse correlations between recovery and mortality rates of COVID-19 patients with vitamin D status in different countries. Considering latitudes, a small reverse correlation between vitamin D status and mortality rate was found globally. It seems that populations with lower levels of vitamin D might be more susceptible to the novel coronavirus infection. Nevertheless, due to multiple limitations, if this study does not allow to quantify a value of the Vitamin D with full confidence, it allows at least to know what the Vitamin D might be and that it would be prudent to invest in this direction through comprehensive large randomized clinical trials.

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

“…Ghasemian et al, conducted a formal systematic review of nine studies, with six studies entering into a meta-analyses, and added their own evaluation of the correlation between global vitamin D status and COVID-19 recovery and mortality ( 70 ). The meta-analysis revealed that 46.5% of COVID-19 patients were vitamin D deficient and an additional 43.3% were vitamin D insufficient ( 70 ).…”

“…Mitchell's brief review (20 May 2020) in a Lancet-affiliated online journal also supported the vitamin D hypothesis (69). Authors of an early meta-analysis of nine studies found that a high percentage of COVID-19 patients are either vitamin D insufficient or deficient, and that countries with lower population vitamin D status have somewhat higher COVID-19 mortality rates and somewhat lower COVID-19 recovery rates (70). In Qatar, vitamin D for prevention of COVID-19 is being proactively delivered to the homes of high-risk diabetics (71).…”

“…Heaney et al, supported the higher level in a reply, citing a recent supplementation study which supported an RDA closer to 7,000 IU/day (97). All three groups used the goal of 20 ng/ml for musculoskeletal health (70). In contrast, the Endocrine Society, aiming to optimize immune health and other aspects of vitamin D function, recommends adults take in 1,500-2,000 IU per day to maintain a 25(OH)D level of 30 ng/ml; 30 ng/ml is the NIH target level as well (29,87).…”

Association of 25 Hydroxyvitamin D Concentration with Risk of COVID-19: A Mendelian Randomization Study

“…However, one study used causal inference analysis, supported the hypothesis that vitamin D plays a causal role in COVID-19 outcomes via modi cation of host responses to SARS-CoV-2 (24). In addition, there were also systematic reviews and meta-analyses to explore the association between vitamin D and COVID-19 (9,10,25). These studies provided a biological hypothesis and evolving epidemiological data supporting a role for vitamin D in COVID-19.…”

“…vitamin D de ciency contributes to the seasonal increase of virus infections of the respiratory tract, from the common cold to in uenza, and now possibly also COVID-19 (7,8). Some systematic reviews indicated that vitamin D de ciency may increase infection risk of COVID-19 by discussing the biological mechanism of virus infection (2,9,10). In addition, numerous population-based studies have evaluated the Vitamin D de ciency in COVID-19 patients relative to controls; however, the ndings have been inconsistent.…”