Background To investigate the association between serum 25-hydroxyvitamin D levels and its effect on adverse clinical outcomes, and parameters of immune function and mortality due to a SARS-CoV-2 infection. Study design The hospital data of 235 patients infected with COVID-19 were analyzed. Results Based on CDC criteria, among our study patients, 74% had severe COVID-19 infection and 32.8% were vitamin D sufficient. After adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, inpatient mortality serum levels of C-reactive protein (CRP) and an increase in lymphocyte percentage. Only 9.7% of patients older than 40 years who were vitamin D sufficient succumbed to the infection compared to 20% who had a circulating level of 25(OH)D< 30 ng/ml. The significant reduction in serum CRP, an inflammatory marker, along with increased lymphocytes percentage suggest that vitamin D sufficiency also may help modulate the immune response possibly by reducing risk for cytokine storm in response to this viral infection.

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The aims of this randomized controlled double-blind clinical trial were to assess the impact of vitamin D supplementation on calcium metabolism and non-calcemic broad gene expression by relating them to the individual’s responsiveness to varying doses of vitamin D3. Thirty healthy adults were randomized to receive 600, 4,000 or 10,000 IU/d of vitamin D3 for 6 months. Circulating parathyroid hormone (PTH), 25(OH)D, calcium and peripheral white blood cells broad gene expression were evaluated. We observed a dose-dependent increase in 25(OH)D concentrations, decreased PTH and no change in serum calcium. A plateau in PTH levels was achieved at 16 weeks in the 4000 and 10,000 IU/d groups. There was a dose-dependent 25(OH)D alteration in broad gene expression with 162, 320 and 1289 genes up- or down-regulated in their white blood cells, respectively. Our results clearly indicated that there is an individual’s responsiveness on broad gene expression to varying doses of vitamin D3. Vitamin D3 supplementation at 10,000 IU/d produced genomic alterations several fold higher than 4,000 IU/d even without further changes in PTH levels. Our findings may help explain why there are some inconsistency in the results of different vitamin D’s clinical trials.

Objective The goal of this randomized placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D 3 [25(OH)D 3 ] in improving vitamin D status in vitamin D deficient/insufficient patients infected with the SARS-CoV-2 (COVID-19) virus. Methods This is a multicenter randomized double blinded randomized placebo-controlled clinical trial. Participants were recruited from three hospitals that are affiliated to [Institution Blinded for Review], and [Institution Blinded for Review]. Results A total 106 hospitalized patients who had a circulating concentration of 25(OH)D <30 ng/ml were enrolled in this study. Within 30 and 60 days 79.4% (26 out of 34) and 100% (24 out of 24) of the patients who received 25(OH)D 3 became sufficient whereas ≤12.5% the patients in the placebo group became sufficient during 2 months follow-up. We observed an overall lower trend for hospitalization, ICU duration, needing ventilator assistance and mortality in the 25(OH)D3 group compared with placebo group but they weren’t statistically significant. Treatment with oral 25(OH)D 3 was associated with a significant increase in the lymphocyte percentage and decrease in the ratio of neutrophils to lymphocytes (NLR) in the patients. The lower NLR was significant associated with reduced ICU admission days and mortality. Conclusion Our analysis indicated that oral 25-hydroxyvitamin D 3 was able to correct vitamin D deficiency/insufficiency in COVID-19 patients that resulted in improved immune function by increasing blood lymphocyte percentage. RCTs with a larger sample size and with higher dose of 25(OH)D3 maybe needed to confirm the potential effect of 25(OH)D3 on reducing clinical outcomes in COVID-19 patients. Ethics and Dissemination The study protocol was approved by the Ethics Committee of [Institution Blinded for Review]. (Approval Number: IR.TUMS.VCR.REC.1399.061). Dissemination plans include academic publications, conference presentations and social media. Trial registration The protocol was registered with the Iranian Registry of Clinical Trials (IRCT) on April 11, 2020 [Number Blinded for Review]. and U.S. National Institutes of Health [Number Blinded for Review] on May 11, 2020.

Background/Aim: To investigate the effects of vitamin D 3 supplementation on gut microbiota. Patients and Methods: Twenty adults with vitamin D insufficiency/deficiency [25(OH)D <30 ng/ml] were enrolled and given 600, 4,000 or 10,000 IUs/day of oral vitamin D 3 . Stool samples were collected at baseline and 8 weeks for identifying gut microbiota using 16S rRNA gene amplification and sequencing. Results: Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (p<0.05). After the intervention, we observed a dose-dependent increase in relative abundance of Bacteroides with a significant difference between the 600 IUs and the 10,000 IUs groups (p=0.027), and Parabacteroides with a significant difference between the 600 IUs and the 4,000 IUs groups (p=0.039). Conclusion: Increased serum 25(OH)D was associated with increased beneficial bacteria and decreased pathogenic bacteria. A dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity was observed after vitamin D 3 supplementation. Patients and MethodsHealthy adults who had vitamin D insufficiency/deficiency [25(OH)D<30 ng/ml] were enrolled in a randomized, doubleblinded, investigator initiated, pilot study. This study investigated broad gene expression changes in peripheral blood mononuclear cells following vitamin D 3 supplementation of 600, 4,000 or 10,000 IU/day of vitamin D 3 , as previously described (11). The study was 551

Vitamin D is known not only for its importance for bone health, but also for its biologic activities on other many other organ systems. This is due to the presence of the vitamin D receptor (VDR) in various types of cells and tissues, including the skin, skeletal muscle, adipose tissue, endocrine pancreas, immune cells and blood vessels. Experimental studies have shown that vitamin D exerts several actions that are thought to be protective against COVID-19 infectivity and severity. These include the immunomodulatory effects on the innate and adaptive immune systems, the regulatory effects on renin-angiotensin-aldosterone-system in the kidneys and the lungs, and the protective effects against endothelial dysfunction and thrombosis. Prior to the COVID-19 pandemic, studies have shown that vitamin D supplementation is beneficial in protecting against risk of acquiring acute respiratory viral infection and may improve outcomes in sepsis and critically ill patients. There are a growing number of data connecting COVID-19 infectivity and severity with vitamin D status, suggesting a potential benefit of vitamin D supplementation for primary prevention or as an adjunctive treatment of COVID-19. Although the results from most ongoing randomized clinical trials aiming to prove the benefit of vitamin D supplementation for these purposes are still pending, there is no downside to increasing vitamin D intake and having sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at least 30 ng/mL (75 nmol/L) and preferably at 40 – 60 ng/mL (100 – 150 nmol/L) to minimize the risk of COVID-19 infection and its severity.

Objective To determine the association between vitamin D status and morbidity and mortality in adult hospitalized COVID-19 patients Methods We performed a retrospective chart review study in COVID-19 patients aged ≥18 years old hospitalized at Boston University Medical Center between March 1 – August 4, 2020. All studied patients were tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D results measured within one year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and were analyzed to determine the association between vitamin D status and hospital morbidity and mortality. Results Among the 287 patients, 100 (36%) patients were vitamin D-sufficient [25(OH)D >30 ng/mL] and 41 (14%) patients died during the hospitalization. Multivariate analysis in patients aged ≥65 years old revealed that vitamin D sufficiency [25(OH)D ≥30 ng/mL] was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95%CI, 0.12–0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95%CI, 0.05–0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95%CI, 0.08–0.88), after adjustement for potential confounders. Among patients with body mass index <30 kg/m 2 , vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95%CI, 0.04–0.84). No significant association was found in the subgroups of patients aged <65 years old or BMI ≥30 kg/m 2 . Conclusion We revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.

Background/Aim: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D 3 . Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D 3 /day for 6 months. Circulating parathyroid hormone (PTH), 25hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. Results: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D 3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. Conclusion: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.