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Background Evidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID‐19. Hence, we carried out a systematic review and meta‐analysis in order to maximise 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 and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID‐19 patients were entered into the systematic review. Results Twenty‐three studies containing 11 901 participants entered into the meta‐analysis. The meta‐analysis indicated that 41% of COVID‐19 patients were suffering from vitamin D deficiency (95% CI, 29%‐55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%‐63%). The serum 25‐hydroxyvitamin D concentration was 20.3 ng/mL among all COVID‐19 patients (95% CI, 12.1‐19.8). The odds of getting infected with SARS‐CoV‐2 are 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5‐4.3). The chance of developing severe COVID‐19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6‐10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5‐4.4). Conclusion This study found that most of the COVID‐19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS‐CoV‐2 among vitamin‐D‐deficient individuals and about five times higher probability of developing the severe disease in vitamin‐D‐deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

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.

Introduction. Streptococcus pneumoniae is a significant bacterial pathogen in humans. Currently, there are two types of pneumococcal vaccines, but there are concerns regarding their application. Aim. Since many pneumococcal proteins are serotype-independent, polyhistidine triad protein D (PhtD) has been selected as a vaccine candidate. Methodology. We prepared recombinant PhtD and its C-terminal fragment (PhtD-C) using alum and outer-membrane vesicles (OMVs) as adjuvants. The combinations were injected intraperitoneally into mice, and then total immunoglobulin G (IgG) and specific IgG, IgG1 and IgG2a were measured. A serum bactericidal assay and opsonophagocytosis were also performed as complementary tests. Meningococcal OMVs were used as an adjuvant. Results. The levels of specific IgG and IgG1 against combinations of PhtD and its C-terminal with OMVs and alum as adjuvants increased at the time of the third mouse immunization on day 35. Forty per cent and 60% of S. pneumoniae ATCC 6303 (serotype 3) as a virulent pneumococcal strain, respectively, were killed in the opsonophagocytosis test and these results could also be observed in the serum bactericidal assay. Mice mmunized iwith PhtD and its C-terminal with OMVs and alum as adjuvants survived after 10 days of pneumococcal challenge. Conclusion. The combination of PhtD and PhtD-C with alum produced optimal results, but the combination of PhtD and PhtD-C with OMVs produced minimal results by comparison. The survival rates were also measured, and these corresponded with the results of the immunological assessments. Our findings showed that mice receiving PhtD and PhtD-C plus OMV and alum had higher survival rates than the mice in the other groups.