Evaluation of the safety and efficacy of AdvaxTM as an adjuvant: A systematic review and meta-analysis.

PURPOSE: Developing a vaccine with improved immunogenicity is still a growing priority for many diseases. Different types of adjuvants may be beneficial to initiate and maintain the long-lasting immunogenicity of vaccines. Evidence has shown that polysaccharide adjuvants are efficient in improving immunological mechanisms with their biocompatibility and biodegradability characteristics. In this study, we aimed to investigate the safety and efficacy of AdvaxTM an adjuvant derived from delta inulin. METHODS: A systematic research was performed in Pubmed, Web of Science, and Scopus databases for the following keywords; "AdvaxTM" OR "delta inulin" until December 14th, 2020. RevMan 5.4.1 software was used for cumulative meta-analysis and bias analysis. We also used GraphPad Prism 6 software for the figures. RESULTS: In the cumulative meta-analysis, it was found that seroconversion and geometric mean titers (GMT) levels significantly increased in AdvaxTM-adjuvanted group (mean difference: 12.31, 95% Cl [4.14, 20.47], p â€‹= â€‹0.003; 17.10, 95% Cl [4.35, 29.85], p â€‹= â€‹0.009, respectively). We also observed that AdvaxTM could be effective in improving immunogenicity by inducing T-cell responses and plasmablast generation in viral vaccines. CONCLUSIONS: In this study, it was shown that AdvaxTM is a safe and well-tolerated adjuvant. AdvaxTM could be a potent adjuvant in increasing the protection and immunogenicity of different vaccines without safety issues. However, further studies are needed to verify these effects of AdvaxTM adjuvant.

Serum midkine level might be a diagnostic tool for COVID19 disease in pregnancy: From the disease severity, hospitalization and disease progression respects.

BACKGROUND: New biomarkers for diagnosis and monitoring the COVID-19 disease are the most important topics to be studied recently. We aimed to investigate the association between midkine levels and disease severity in pregnant women with COVID-19. METHODS: Totally 186 pregnant women were participated in this study. 96 of them were healthy pregnant women, 90 of them were pregnant women with COVID19. Pregnant women were evaluated according to their trimesters. Serum midkine level, biochemical profile clinical and disease severity outcomes of pregnant women were obtained. RESULTS: Our results showed that pregnant women with COVID19 have significantly increased serum midkine level compared to healthy pregnant women (1.801 ± 0.977 vs 0.815 ± 0.294 ng/dL). According to the data among each trimester, it was shown that there were significant increase in serum midkine level during all pregnancy trimesters (1st trimester Control Group: 0.714 ± 0.148, COVID-19 group 1.623 ± 0.824, p < 0.0001; 2nd trimester Control Group: 0.731 ± 0.261, COVID-19 group 2.059 ± 1.146, p < 0.0001; 3rd trimester Control Group: 1.0 ± 0.35, COVID-19 group 1.723 ± 0.907, p = 0.001). Serum midkine levels were significantly different between disease severity subgroups of pregnant women with COVID19; moderate and severe/critic groups had significantly higher serum midkine level than mild group. There was also significant correlation between serum midkine level and severity status (p:0.0001, r: 0.468). The most striking results of serum midkine levels were corelation between length of hospitalization (p: 0.01, r: 0.430) and O2 saturation (p < 0.0001, r: -0.521). ROC curve analysis showed that serum midkine level might be a tool for predicting COVID-19 in pregnant women with COVID-19 (AUC: 0.912, 95% CI: [0.871, 0.952], p < 0.0001) CONCLUSION: Our data showed that there is an obvious relation between COVID19 progression and serum midkine level for the first time which might be used for monitoring the disease process.

Maternal selenium status plays a crucial role on clinical outcomes of pregnant women with COVID-19 infection.

Adequate maternal selenium level is essential for immune response and healthy pregnancy. This study aimed to shed light on the selenium status of pregnant women with COVID-19 and the effects of potential deficiency in serum selenium levels. Totally 141 pregnant women, 71 of them were COVID-19 patients, in different trimesters were included in the study. Maternal serum selenium levels, demographic and clinical parameters were determined. Serum selenium levels of pregnant women in the second (p: .0003) and third (p: .001) trimesters with COVID-19 were significantly lower than in the healthy group. Maternal selenium level was found to be negatively correlated with gestational week (p < .0001, r: -.541), D-dimer (p: .0002, r: -.363) and interleukin-6 (IL-6) level (p: .02, r: -.243). In the second trimester, serum selenium level positively correlated with white blood cell (p: .002, r: .424), neutrophil (p: .006, r: .39), lymphocyte (p: .004, r: .410) count and hemoglobin (p: .02, r: .323), hematocrit (p: .008, r: .38) status. In the third trimester, it was found that maternal selenium level positively correlated with monocyte (p: .04, r: .353) and negatively correlated with C-reactive protein level (p: .03, r: -.384). Serum selenium level was gradually decreased during the pregnancy period, however, this natural decrease was enhanced together with COVID-19 infection. The reason might be increased selenium needs depended on the immune response against infection. The decrease in maternal selenium level was found to be related to IL-6 and D-dimer levels, which indicate selenium's role in disease progression.

The Effects of Zinc Supplementation on C-Reactive Protein and Inflammatory Cytokines: A Meta-Analysis and Systematical Review.

Zinc is known for anti-inflammatory and antioxidant roles. In this meta-analysis, we aim to evaluate the impact of zinc supplementation on inflammatory markers, acute-phase reactants, and serum zinc level during inflammatory and infectious diseases. PubMed, Scopus, and Web of Science databases were screened systematically with the terms "zinc supplementation" AND "CRP" OR "IL-1ß" OR "IL-2" OR "IL-6" OR "IL-10" OR "IL-12" OR "TNF-α" OR "TGF-ß" OR "IFN-γ" OR "WBC (clinical trial)" OR "macrophage (clinical trial)" OR "lymphocyte (clinical trial)" OR "neutrophil (clinical trial)" OR "virus (clinical trial)" OR "antiviral (clinical trial)" for all databases. A total of 2,258 publications were screened, and 73 articles had suitable data for the meta-analysis. Serum zinc level was significantly higher in supplementation group compared with controls [P = 0.0006, mean difference: 11.35 (4.84, 17.87)] (n = 37). Zinc supplementation downregulates acute-phase reactants, especially serum C-reactive protein (CRP) in adults [P < 0.00001, mean difference: -0.75 (-0.98, -0.52)] (n = 22) and pregnant women [FEM P < 0.00001, mean difference: -1.77 (-2.53, -1.00)] (n = 3) but not in children [REM P = 0.10, mean difference: -0.85 (-1.86, 0.17)] (n = 3). In subgroups analysis of chronic inflammatory diseases, serum CRP [REM P < 0.00001, mean difference: -0.57 (-0.76, -0.38)] were significantly lower in zinc-supplemented patients compared with no intervention group. Zinc supplementation (mg/day) correlated with serum interferon-gamma (IFN-γ) level (P = 0.018, r = 1,000). In the nonsupplemented group, serum zinc correlated with serum interleukin-6 (IL-6) level (P = 0.041, r = -0.829) and serum tumor necrosis factor alpha (TNF-α) level (P = 0.063, r = 0.730). Zinc intake correlated with serum zinc (P = 0.0428, r = 0.5115) and TNF-α (P = 0.0043, r = -0.9461). This meta-analysis shows that zinc supplementation improves CRP levels in adults and pregnant women. It might have modulatory effects on cytokine secretions and blood cells in inflammatory and infectious diseases. For the first time, we investigated the effects of zinc supplementation on inflammatory cytokine.

Is Zinc an Important Trace Element on Bone-Related Diseases and Complications? A Meta-analysis and Systematic Review from Serum Level, Dietary Intake, and Supplementation Aspects.

Bone-related diseases are very common problems, especially in the elderly population. Zinc takes part in the growth and maintenance of healthy bones. This meta-analysis aims to evaluate the effects of zinc supplementation or dietary zinc intake on serum zinc levels and bone turnover markers. A systematical research was performed with 2899 articles in PubMed, WoS, and Scopus for relevant articles in English which have mean/standard deviation values of serum zinc levels, dietary zinc intake/zinc supplementation (mg/day), and bone turnover markers up to February 2020. In the overall analysis, serum zinc level was significantly lower in patients with osteoporosis compared with controls (p 0.0002). Dietary zinc intake decreased in the fracture group compared with controls according to subgroup analysis patients with fracture (p 0.02). Zinc supplementation was effective on the femoral neck (p < 0.0001) and lumbar spine (p 0.05) bone mineral density (BMD). In the correlation analysis of the data obtained from all of the included studies, serum osteocalcin (p 0.0106, r - 0.9148) correlated with serum zinc level. In conclusion, serum zinc level and dietary zinc intake could have an essential role in preventing osteoporosis. Zinc supplementation might improve bone turnover markers for bone formation such as serum osteocalcin and serum alkaline phosphatase and also, BMD at the site of the femoral neck.