The Role of Vitamin D in The Age of COVID-19: A Systematic Review and Meta-Analysis Along with an Ecological Approach (preprint)

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.

Liver Function in Novel Coronavirus Disease (COVID-19): A Systematic Review and Meta-Analysis (preprint)

Introduction:The outbreak of new coronavirus has become a global public health challenge. Given a consequential liver function, and the high risk of death coming from liver disorders, the assessment of Novel Coronavirus Disease on liver function is importance. Hence, we carried out this meta-analysis to heightening insight into the occult features of COVID 19, which is likely to affect liver function. Method:This study was performed using databases of Web of Science, Scopus, and PubMed. We considered English cross-sectional and case-series papers, which reported available findings on the association between liver injury and COVID-19 infection. We used the STATA v.11 and random effect model for data analysis. Result:In this present meta-analysis, 52 papers, including 8,463 COVID-19 patients, were studied. The prevalence of increased liver enzymes among the patients, including Alanine aminotransferase, Aspartate aminotransferase, were 30% and 21% in non-severe patients, respectively, which were 38% and 48% in severe patients. The prevalence of increasing C-reactive protein, Lactate dehydrogenase, D-dimer, and Bilirubin were 55%, 39%, 28%, and 10% in non-severe patients respectively, which were 78%, 75%, 79% and 17% in sever patients.The prevalence of liver toxicity as a complication of COVID-19 was 20%.Also patients who have severe condition are 5.54, 4.22, 4.96, 4.13 and 4.34 times more likely to have elevated CRP, ALT, AST, LDH, D-dimer enzymes retrospectively. Conclusion:Elevation of some liver markers were higher in patients with severe COVID-19 infection. All to gather, we assumed that abnormal liver markers could act as a prognostic factor for a better survey of COVID-19.