The association between the level of serum 25(OH) vitamin D, obesity, and underlying diseases with the risk of developing COVID-19 infection: A case-control study of hospitalized patients in Tehran, Iran.

BACKGROUND AND OBJECTIVES: The outbreak of COVID-19 has created a global public health crisis. Little is known about the predisposing factors of this infection. The aim of this study was to explore an association between the serum vitamin D level, obesity, and underlying health conditions, as well as the vulnerability to COVID-19 in the Iranian population. METHODS: We conducted a case-control study of 201 patients with coronavirus infection and 201 controls. Cases and controls were matched for age and gender. The study was carried out for 2 months (February 2020-April 2020) at Imam Khomeini Hospital Complex, Tehran, Iran. Serum 25(OH) vitamin D was measured using the enzyme-linked immunosorbent assay method. Information containing age, gender, clinical symptoms, body mass index, computed tomography scan findings, and underlying health conditions related to each participant were elicited from health records. RESULTS: A significant negative correlation (p = .02) was observed between the serum vitamin D level and developing coronavirus infection. Also, the results showed that the COVID-19 cases were more likely to be overweight than the controls (p = .023). Diabetes mellitus, hypertension, and respiratory infections were found in 20.89%, 9.65%, and 6.96% of cases, respectively. These underlying health conditions were not significantly different between cases and controls (p = .81). CONCLUSIONS: Vitamin D deficiency and obesity are two main predisposing factors associated with the vulnerability to coronavirus infection in the Iranian population.

Vitamin D insufficiency as a potential culprit in critical COVID-19 patients.

BACKGROUND: As an immune modulator, vitamin D has been implicated in the coronavirus disease-2019 (COVID-19) outcome. We aim to systematically explore the association of vitamin D serum levels with COVID-19 severity and prognosis. METHODS: The standardized mean difference (SMD) or odds ratio and 95% confidence interval (CI) were applied to estimate pooled results from six studies. The prognostic performance of vitamin D serum levels for predicting adverse outcomes with detection of the best cutoff threshold was determined by receiver operating characteristic curve analysis. Decision tree analysis by combining vitamin D levels and clinical features was applied to predict severity in COVID-19 patients. RESULTS: Mean vitamin D serum level of 376 patients, was 21.9 nmol/L (95% CI = 15.36-28.45). Significant heterogeneity was found (I2 = 99.1%, p < .001). Patients with poor prognosis (N = 150) had significantly lower serum levels of vitamin D compared with those with good prognosis (N = 161), representing an adjusted standardized mean difference of -0.58 (95% Cl = -0.83 to -0.34, p < .001). CONCLUSION: Serum vitamin D levels could be implicated in the COVID-19 prognosis. Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients' potential of developing severe COVID-19. Appropriate preventative and/or therapeutic intervention may improve COVID-19 outcomes.

Role of vitamin D in treating COVID-19-associated coagulopathy: problems and perspectives.

Aggressive inflammatory response leading to hypercoagulability has been found to be associated with disease severity in COVID-19 patients and portends bad treatment outcome. A state of acute disseminated intravascular coagulation (DIC), along with pulmonary embolism and/or deep vein thrombosis, has been observed in critically ill ICU patients. Autopsy reports of COVID-19 patients demonstrated microthrombi in lungs and in other organs, as well as marked inflammatory changes, characteristic clinicopathological features that exacerbate disease severity. Vitamin D supplementation was recommended by many clinicians across the globe to improve clinical symptoms of COVID-19 patients, mainly because of its immunomodulatory roles on immune cells. Furthermore, vitamin D and its associated molecules are also known to directly or indirectly regulate various thrombotic pathways. We propose that vitamin D supplementation not only attenuates the risk of Acute Respiratory Disease Syndrome (ARDS) but it also may have a role in reducing coagulation abnormalities in critically ill COVID-19 patients. The overarching goal of this review is to discuss the effects of vitamin D on coagulation pathways and other intertwined processes leading to thrombosis. Many clinical trials are currently investigating the efficacy of vitamin D supplementation in reducing the risk of COVID-19 infection. However, randomized placebo control clinical trials are also necessary to ascertain the effect of vitamin D supplementation on reducing the risk of coagulopathy in COVID-19 patients.

l-Cysteine Stimulates the Effect of Vitamin D on Inhibition of Oxidative Stress, IL-8, and MCP-1 Secretion in High Glucose Treated Monocytes.

Objective: Vitamin D deficiency is common in the general population and diabetic patients, and supplementation with vitamin D is widely used to help lower oxidative stress and inflammation. The cytokine storm in SARS-CoV2 infection has been linked with both diabetes and Vitamin D deficiency. This study examined the hypothesis that supplementation with vitamin D, in combination with l-cysteine (LC), is better at reducing oxidative stress and thereby, more effective, at inhibiting the secretion of the pro-inflammatory cytokines, Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in U937 monocytes exposed to high glucose concentrations. Methods: U937 monocytes were pretreated with 1,25 (OH)2 vitamin D (VD, 10 nM) or LC (250 µM) or VD + LC for 24 h and then exposed to control or high glucose (HG, 25 mM) for another 24 h. Results: There were significantly greater reactive oxygen species (ROS) levels in monocytes treated with HG than those in controls. Combined supplementation with VD and LC showed a more significant reduction in ROS (46%) in comparison with treatment with LC (19%) or VD (26%) alone in monocytes exposed to HG. Similarly, VD supplementation, together with LC, caused a more significant inhibition in the secretion of IL-8 (36% versus 16%) and MCP-1 (46% versus 26%) in comparison with that of VD (10 nM) alone in high-glucose treated monocytes. Conclusions: These results suggest that combined supplementation with vitamin D and LC has the potential to be more effective than either VD or LC alone in lowering the risk of oxidative stress and inflammation associated with type 2 diabetes or COVID-19 infection. Further, this combined vitamin D with LC/N-acetylcysteine may be a potent alternative therapy for SARS-CoV2 infected subjects. This approach can prevent cellular damage due to cytokine storm in comorbid systemic inflammatory conditions, such as diabetes, obesity, and hypertension.

Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19.

BACKGROUND: The severity of Coronavirus Disease 2019 (COVID-19) is a multifactorial condition. An increasing body of evidence argues for a direct implication of vitamin D deficiency, low serum calcium on poor outcomes in COVID-19 patients. This study was designed to investigate the relationship between these two factors and COVID-19 in-hospital mortality. MATERIALS: This is a prospective study, including 120 severe cases of COVID-19, admitted at the department of Reanimation-Anesthesia. Vitamin D was assessed by an immuno-fluoroassay method. Total serum calcium by a colorimetric method, then, corrected for serum albumin levels. The association with in-hospital mortality was assessed using the Kaplan-Meier survival curve, proportional Cox regression analyses and the receiver operating characteristic curve. RESULTS: Hypovitaminosis D and hypocalcemia were very common, occurring in 75% and 35.8% of patients. When analyzing survival, both were significantly associated with in-hospital mortality in a dose-effect manner (pLog-Rank = 0.009 and 0.001 respectively). A cutoff value of 39 nmol/l for vitamin D and 2.05 mmol/l for corrected calcemia could predict poor prognosis with a sensitivity of 76% and 84%, and a specificity of 69% and 60% respectively. Hazard ratios were (HR = 6.9, 95% CI [2.0-24.1], p = 0.002 and HR = 6.2, 95% CI [2.1-18.3], p = 0.001) respectively. CONCLUSION: This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that the correction of hypocalcemia, as well as supplementation with vitamin D, may improve the vital prognosis.

Prevalence and Clinical Outcomes of Vitamin D Deficiency in COVID-19 Hospitalized Patients: A Retrospective Single-Center Analysis.

Vitamin D attenuates inflammatory responses to viral respiratory infections. Hence, vitamin D deficiency may be a highly significant prognostic factor for severity and mortality in COVID-19 patients. To evaluate the complications and mortality in different vitamin D status groups in COVID-19 hospitalized patients, we conducted this retrospective study on 646 laboratory-confirmed COVID-19 patients who were hospitalized in Shahid Modarres Hospital, Tehran, Iran from 16th March 2020 until 25th February 2021. Overall, patients with vitamin D deficiency, insufficiency and sufficiency were 16.9%, 43.6% and 39.5%, respectively. The presence of comorbidity, length of hospitalization, ICU admission, and invasive mechanical ventilation requirement and overall complications were significantly more in patients with vitamin D deficiency (p-value < 0.001). 46.8% (51/109) of vitamin D deficient patients died due to the disease, whilst the mortality rate among insufficient and sufficient vitamin D groups was 29.4% (83/282) and 5.5% (14/255), respectively. In univariate analysis, age > 60 years (odds ratio (OR) = 6.1), presence of comorbidity (OR = 10.7), insufficient vitamin D status (OR = 7.2), and deficient vitamin D status (OR = 15.1) were associated with increase in COVID-19 mortality (p-value < 0.001). Finally, the multivariate analysis adjusted for age, sex, and comorbidities indicated vitamin D deficiency as an independent risk factor for mortality (OR = 3.3, p-value = 0.002). Vitamin D deficiency is a strong risk factor for mortality and severity of SARS-CoV-2 infection. Vitamin D supplementation may be able to prevent or improve the prognosis of COVID-19 during this pandemic.

The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has led to a declaration of a Public Health Emergency of International Concern by the World Health Organization. As of May 18, 2020, there have been more than 4.7 million cases and over 316,000 deaths worldwide. COVID-19 is caused by a highly infectious novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to an acute infectious disease with mild-to-severe clinical symptoms such as flu-like symptoms, fever, headache, dry cough, muscle pain, loss of smell and taste, increased shortness of breath, bilateral viral pneumonia, conjunctivitis, acute respiratory distress syndromes, respiratory failure, cytokine release syndrome (CRS), sepsis, etc. While physicians and scientists have yet to discover a treatment, it is imperative that we urgently address 2 questions: how to prevent infection in immunologically naive individuals and how to treat severe symptoms such as CRS, acute respiratory failure, and the loss of somatosensation. Previous studies from the 1918 influenza pandemic have suggested vitamin D's non-classical role in reducing lethal pneumonia and case fatality rates. Recent clinical trials also reported that vitamin D supplementation can reduce incidence of acute respiratory infection and the severity of respiratory tract diseases in adults and children. According to our literature search, there are no similar findings of clinical trials that have been published as of July 1st, 2020, in relation to the supplementation of vitamin D in the potential prevention and treatment for COVID-19. In this review, we summarize the potential role of vitamin D extra-renal metabolism in the prevention and treatment of the SARS-CoV-2 infection, helping to bring us slightly closer to fulfilling that goal. We will focus on 3 major topics here: 1. Vitamin D might aid in preventing SARS-CoV-2 infection: Vitamin D: Overview of Renal and Extra-renal metabolism and regulation. Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis. Vitamin D: Overview of local immunomodulation in human infectious diseases. Anti-viral infection. Anti-malaria and anti-systemic lupus erythematosus (SLE). 2. Vitamin D might act as a strong immunosuppressant inhibiting cytokine release syndrome in COVID-19: Vitamin D: Suppression of key pro-inflammatory pathways including nuclear factor kappa B (NF-kB), interleukin-6 (IL-6), and tumor necrosis factor (TNF). 3. Vitamin D might prevent loss of neural sensation in COVID-19 by stimulating expression of neurotrophins like Nerve Growth Factor (NGF): Vitamin D: Induction of key neurotrophic factors. .

Maternal plasma vitamin D levels and associated determinants in late pregnancy in Harare, Zimbabwe: a cross-sectional study.

BACKGROUND: The importance of vitamin D in bone health and calcium homeostasis has been well documented. However, emerging evidence supports the role of vitamin D beyond its recognised traditional roles. In pregnancy, vitamin D levels are crucial in sustaining both the maternal stores and optimal growth of the foetus. In Southern Africa, there is paucity of data on vitamin D in pregnancy and related outcomes. To expand this body of knowledge, we assessed vitamin D levels in late pregnancy and (if any) associated maternal determinants in Harare, Zimbabwe. METHODS: Study participants comprised of 138 pregnant Zimbabwean women in their third trimester. These were stratified by HIV status; sampling median (IQR) gestation for HIV negative study participants was 34 weeks (26-41) and 31 weeks (20-40) in the HIV positive participants. Maternal plasma 25 hydroxyvitamin (OH) Dlevels were measured using the ClinPrepHigh Pressure Liquid Chromatography (HPLC) kit. Statistical analysis was carried out using the STATA statistical package version 13. A p-value of < 0.05was considered to be statistically significant. RESULTS: HIV infected participants had significantly higher mean 25 (OH) D concentration (112 ± 33.4 nmol/L) compared to the HIV uninfected (100 ± 27.1 nmol/L), p = 0.032.Participants whose samples were collected during summer had higher maternal 25 (OH) D levels than those cART duration and maternal 25 (OH) D levels (p = 0.031, Spearman correlation =0.28). CONCLUSIONS: Our findings show high mean levels of maternal 25 (OH) D in late pregnancy in our setting and in the absence of vitamin D supplementation. Both HIV infection and season are significant determinants of maternal vitamin D levels. Summer season is associated with higher maternal plasma 25 (OH) D levels. HIV infection is associated with increased maternal vitamin D levels. Prolonged use of cART, Tenolam E is associated with improved maternal 25(OH) D levels.

Effect of high-dose cholecalciferol (vitamin D3) on bone and body composition in children and young adults with HIV infection: a randomized, double-blind, placebo-controlled trial.

It is unknown whether vitamin D supplementation positively impacts body composition and bone outcomes in children and young adults with HIV. This RCT found that despite increasing 25(OH)D concentrations, high dose vitamin D3 supplementation did not impact bone or body composition in children and young adults with HIV infection. INTRODUCTION: The objective of this paper was to determine the impact of high-dose daily cholecalciferol (vitamin D3) supplementation on body composition and bone density, structure, and strength in children and young adults with perinatally acquired (PHIV) or behaviorally acquired (BHIV) HIV infection. METHODS: Participants were randomized to receive vitamin D3 supplementation (7000 IU/day) or placebo for 12 months. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, dual energy X-ray absorptiometry (DXA) of the whole body and lumbar spine, and peripheral quantitative computed tomography (pQCT) of tibia sites were acquired at 0, 6, and 12 months. DXA and pQCT outcomes were expressed as sex- and population-ancestry specific Z-scores relative to age and adjusted for height or tibia length, as appropriate. RESULTS: Fifty-eight participants (5.0 to 24.9 years) received vitamin D3 supplements (n = 30) or placebo (n = 28). At enrollment, groups were similar in age, sex, population ancestry, growth status, serum 25(OH)D concentrations, body composition, and size-adjusted bone measures. Median 25(OH)D concentrations were similar (17.3 ng/mL in the vitamin D3 supplementation group vs 15.6 ng/mL in the placebo group), and both groups had mild bone deficits. At 12 months, 25(OH)D rose significantly in the vitamin D supplementation group but not in the placebo group (26.4 vs 14.8 ng/mL, respectively, p < 0.008). After adjusting for population ancestry, sex, antiretroviral therapy use, and season, there were no significant treatment group differences in bone or body composition outcomes. CONCLUSIONS: Despite increasing 25(OH)D concentrations, 12 months of high-dose vitamin D3 supplementation did not impact bone or body composition in children and young adults with HIV infection.

Lack of association between serum 25-hydroxyvitamin D levels and cervical human papillomavirus infection in systemic lupus erythematosus.

Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV.

Prevalence of vitamin D deficiency and insufficiency in Bulgarian patients with chronic hepatitis C viral infection.

AIMS: The present pilot study aimed to determine vitamin D status in Bulgarian patients with chronic HCV infection in respect to the severity of liver disease and response to interferon-ribavirin therapy. METHODS: The study encompassed 296 patients: 161 males (54.4%) aged 42.08 ± 14.87 years, 135 females (45.6%) aged 45.72 ± 14.34 years, 86.5% of them infected with HCV genotype 1. Total 25-hydroxyvitamin-D (25OHD) was determined by liquid chromatography/tandem-mass spectrometric detection. RESULTS: The median 25OHD level of the studied cohort was 50.40 nmol/L (range: 29.6-71.05). 25OHD deficient (< 25 nmol/L) were 16% of patients, 33% showed profound insufficiency (25-50 nmol/L), another 33% were in the range 50-80 nmol/L (mild insufficiency), the rest 18% were 25OHD sufficient. Significantly lower 25OHD levels were registered in cases with advanced fibrosis compared to those with mild or absent fibrosis (37.10 nmol/L vs. 53.00 nmol/L, respectively, p < 0.05). This association remained unchanged by seasonal variations in 25OHD levels. Inverse relationship was found between 25OHD and HCV-RNA (p < 0.01). Patients with sustained virological response to therapy had significantly higher 25OHD levels, compared to patients who failed to achieve viral eradication (56.90 nmol/L vs. 45.00 nmol/L, p = 0.012). CONCLUSION: More than 80% of HCV-infected patients were vitamin D-deficient and -insufficient. The inverse relationship between 25OHD levels and viral load, liver fibrosis and treatment outcomes supports the hypothesis that improvement of vitamin D status may have considerable potential to amend the host defense against HCV infection and response to therapy.

Association of higher plasma vitamin D binding protein and lower free calcitriol levels with tenofovir disoproxil fumarate use and plasma and intracellular tenofovir pharmacokinetics: cause of a functional vitamin D deficiency?

Tenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by an unknown mechanism(s). Data are limited on tenofovir pharmacokinetics and these effects. Using baseline data from a multicenter study of HIV-infected youth on stable treatment with regimens containing TDF (n = 118) or lacking TDF (n = 85), we measured cross-sectional associations of TDF use with markers of renal function, vitamin D-calcium-parathyroid hormone balance, phosphate metabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 [FGF23]), and bone turnover. Pharmacokinetic-pharmacodynamic associations with plasma tenofovir and intracellular tenofovir diphosphate concentrations were explored among those receiving TDF. The mean age was 20.9 (standard deviation [SD], 2.0) years; 63% were male; and 52% were African American. Compared to the no-TDF group, the TDF group showed lower mean estimated glomerular filtration rates and tubular reabsorption of phosphate, as well as higher parathyroid hormone and 1,25-dihydroxy vitamin D [1,25-OH(2)D] levels. The highest quintile of plasma tenofovir concentrations was associated with higher vitamin D binding protein, lower free 1,25-OH(2)D, higher 25-OH vitamin D, and higher serum calcium. The highest quintile of intracellular tenofovir diphosphate concentration was associated with lower FGF23. Higher plasma tenofovir concentrations were associated with higher vitamin D binding protein and lower free 1,25-OH(2)D, suggesting a functional vitamin D deficiency explaining TDF-associated increased parathyroid hormone. The finding of lower FGF23 accompanying higher intracellular tenofovir diphosphate suggests that different mechanisms mediate TDF-associated changes in phosphate handling. Separate pharmacokinetic properties may be associated with distinct TDF toxicities: tenofovir with parathyroid hormone and altered calcium balance and tenofovir diphosphate with hypophosphatemia and FGF23 regulation. (The clinical trial registration number for this study is NCT00490412 and is available online at http://clinicaltrials.gov/ct2/show/NCT00490412.).

Vitamin D deficiency and its association with low bone mineral density, HIV-related factors, hospitalization, and death in a predominantly black HIV-infected cohort.

BACKGROUND: Low bone mineral density (BMD) is common among patients infected with human immunodeficiency virus (HIV) and present in higher rates in black subjects. This study assessed vitamin D levels in HIV cases versus noninfected matched controls to determine if deficiency was associated with BMD and HIV clinical outcomes. METHODS: In total, 271 military beneficiaries with HIV underwent dual energy x-ray absorptiometry (DEXA) screening in 2001-2. Serum 25OH-vitamin D levels were determined using stored serum from the time of DEXA and 6-18 months prior. Two non-HIV-infected controls for each active duty case (n = 205) were matched on age, sex, race, zip code, and season using the Department of Defense Serum Repository (DoDSR). Vitamin D levels <20 ng/mL were considered deficient. HIV-related factors and clinical outcomes were assessed using data collected in the DoD HIV Natural History study. RESULTS: In total, 165 of 205 (80.5%) active duty HIV cases had 2 matched controls available. HIV cases had greater odds of for vitamin D deficiency (VDD) compared with controls (demographics adjusted paired data odds ratio [OR], 1.46, 95% confidence interval [CI], .87-2.45), but this was not statistically significant. Blacks were disproportionately deficient (P <.001) but not relative to HIV status or BMD. Low BMD was associated with typical risk factors (low body mass index and exercise levels, alcohol use); given limited available data the relationship between tenofovir exposure and VDD or low BMD could not be determined. Analysis of HIV-specific factors and outcomes such as exposure to antiretrovirals, HIV progression, hospitalizations, and death revealed no significant associations with vitamin D levels. CONCLUSIONS: VDD was highly prevalent in black HIV- infected persons but did not explain the observed racial disparity in BMD. Vitamin D deficiency was not more common among HIV- infected persons, nor did it seem associated with HIV- related factors/clinical outcomes.

Effects of Vitamin D Supplementation on Bone Health and Bone-related Parameters in HIV-infected Patients: A Systematic Review and Meta-analysis.

PURPOSE: There is growing evidence that bone health is decreased in individuals with HIV infection. Vitamin D deficiency is also highly prevalent among HIV-infected patients. The literature was systematically reviewed to determine whether bone health and bone-related parameters may improve with vitamin D supplementation in HIV-infected individuals. METHODS: Four databases were systematically searched for randomized clinical trials of vitamin D supplementation in HIV infection, published from January 1990 to September 2021. No language or publication restrictions were applied. Standardized mean differences (SMD) with 95% CIs are reported. A random-effects model was used to perform meta-analysis. FINDINGS: Ten studies met the inclusion criteria (N = 733 participants at study completion). The mean ages of the patients in the included trials ranged from 10 to 49 years. The meta-analysis indicated that with vitamin D supplementation, serum 25-hydroxy vitamin D (25[OH]D) level was significantly increased (SMD, 1.86; 95% CI, 1.02 to 2.70; I2 = 94.4%), but there were no significant effects on levels of serum 1,25-dihydroxy vitamin D (1,25-[OH]2D) (SMD, 0.29; 95% CI, -0.07 to 0.64; I2 = 67.4%), total bone mineral density (SMD, 0.07; 95% CI, -0.23 to 0.37; I2 = 00.0%), spine bone mineral density (SMD, 0.15; 95% CI, -0.19 to 0.49; I2 = 17.3%), and parathyroid hormone level (SMD, -0.18; 95% CI, -0.37 to 0.02; I2 = 1.2%) in HIV-infected patients. IMPLICATIONS: This study showed that vitamin D supplementation can improve serum 25(OH)D in HIV-infected patients. The effects of vitamin D supplementation on other bone health-related parameters such as bone mineral density and parathyroid hormone in HIV-infected patients need to be further investigated in larger-scale, well-designed randomized, controlled trials.

Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity.

Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes ß-defensin 2/defensin-ß4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.

Vitamin D in HIV-Infected Patients.

Observational studies have noted very high rates of low 25(OH)D (vitamin D) levels in both the general and HIV-infected populations. In HIV-infected patients, low 25(OH)D levels are likely a combination of both traditional risk factors and HIV-specific and antiretroviral therapy-specific contributors. Because of this unique risk profile, HIV-infected persons may be at greater risk for low 25(OH)D levels and frank deficiency and/or may respond to standard repletion regimens differently than HIV-uninfected patients. Currently, the optimal repletion and maintenance dosing regimens for HIV-infected patients remain unknown, as do potential benefits of supplementation that may be unique to the HIV-infected population. This paper reviews data published on HIV infection and vitamin D health in adults over the last year.

The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis.

Background: Coronavirus disease (COVID-19) is a respiratory and systemic disorder caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or novel Coronavirus (nCoV). To date, there is no proven curative treatment for this virus; as a result, prevention remains to be the best strategy to combat coronavirus infection (COVID-19). Vitamin D deficiency (VDD) has been proposed to play a role in coronavirus infection (COVID-19). However, there is no conclusive evidence on its impact on COVID-19 infection. Therefore, the present review aimed to summarize the available evidence regarding the association between Vitamin D levels and the risk of COVID-19 infection. Methods: A systematic literature search of databases (PUBMED/MEDLINE, Cochrane/Wiley library, Scopus, and SciELO) were conducted from May 15, 2020, to December 20, 2020. Studies that assessed the effect of vitamin D level on COVID-19/SARS-2 infection were considered for the review. The qualities of the included studies were evaluated using the JBI tools. Meta-analysis with a random-effects model was conducted and odds ratio with their 95%CI were reported. This systematic review and meta-analysis are reported according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline. Results: The electronic and supplementary searches for this review yielded 318 records from which, only 14 of them met the inclusion criteria. The qualitative synthesis indicated that vitamin D deficient individuals were at higher risk of COVID-19 infection as compared to vitamin D sufficient patients. The pooled analysis showed that individuals with Vitamin-D deficiency were 80% more likely to acquire COVID-19 infection as compared to those who have sufficient Vitamin D levels (OR = 1.80; 95%CI: 1.72, 1.88). Begg's test also revealed that there was no significant publication bias between the studies (P = 0.764). The subgroup analysis revealed that the risk of acquiring COVID-19 infection was relatively higher in the case-control study design (OR = 1.81). Conclusions: In conclusion, low serum 25 (OH) Vitamin-D level was significantly associated with a higher risk of COVID-19 infection. The limited currently available data suggest that sufficient Vitamin D level in serum is associated with a significantly decreased risk of COVID-19 infection.

Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19.

We evaluated associations between serum 25-hydroxyvitamin D [25(OH)D] level and severity of new coronavirus infection (COVID-19) in hospitalized patients. We assessed serum 25(OH)D level in 133 patients aged 21-93 years. Twenty-five (19%) patients had severe disease, 108 patients (81%) had moderate disease, and 18 (14%) patients died. 25(OH)D level ranged from 3.0 to 97.0 ng/mL (median, 13.5 [25%; 75%, 9.6; 23.3] ng/mL). Vitamin D deficiency was diagnosed in 90 patients, including 37 with severe deficiency. In patients with severe course of disease, 25(OH)D level was lower (median, 9.7 [25%; 75%, 6.0; 14.9] ng/mL), and vitamin D deficiency was more common than in patients with moderate course (median, 14.6 [25%; 75%, 10.6; 24.4] ng/mL, p = 0.003). In patients who died, 25(OH)D was 9.6 [25%; 75%, 6.0; 11.5] ng/mL, compared with 14.8 [25%; 75%, 10.1; 24.3] ng/mL in discharged patients (p = 0.001). Severe vitamin D deficiency was associated with increased risk of COVID-19 severity and fatal outcome. The threshold for 25(OH)D level associated with increased risk of severe course was 11.7 ng/mL. Approximately the same 25(OH)D level, 10.9 ng/mL, was associated with increased risk of mortality. Thus, most COVID-19 patients have vitamin D deficiency; severe vitamin D deficiency is associated with increased risk of COVID-19 severity and fatal outcome.