Significance of 1,25-Dihydroxyvitamin D3 on Overall Mortality in Peritoneal Dialysis Patients with COVID-19.

In previous publications, we pointed out the importance of mannosylation of fibrinogen for the development of cardiovascular complications and fucosylation as a predictor of peritoneal membrane dysfunction in patients on peritoneal dialysis (PD). After a follow-up period of 30 months from the onset of the COVID-19 pandemic, we evaluated the significance of 1,25-dihydroxyvitamin D3 (calcitriol) therapy, primary disease, biochemical and hematologic analyzes, and previously performed glycan analysis by lectin-based microarray as predictors of mortality in this patient group. After univariate Cox regression analysis, diabetes mellitus (DM) and calcitriol therapy were found to be potential predictors of mortality. Additional multivariate Cox regression analysis confirmed that only DM was a predictor of mortality. Nevertheless, the use of calcitriol in therapy significantly reduced mortality in this patient group, as shown by the Kaplan-Meier survival curve. The presence of DM as a concomitant disease proved to be a strong predictor of fatal outcome in PD patients infected with SARS-CoV-2. This is the first study to indicate the importance and beneficial effect of calcitriol therapy on survival in PD patients with COVID-19 infection. In addition, this study points to the possibility that adverse thrombogenic events observed in PD patients during the pandemic may be caused by aberrant fibrinogen glycosylation.

Acute exantematic pustulosis generalized by meropenem, differential diagnosis with COVID

Case report We present the case of a 63-year- old man with two consecutive admissions, due to COVID19 infection and subsequent bacterial superinfection. Three days after the second admission (04/28), and 43 days from the beginning of the infection an assessment by dermatology and allergology is then requested. The patient had generalized erythematous maculopapular rash in the trunk, back, groin and limbs. On the left side and back, pustular lesions not focused on follicles were also added, with a fever of 37.7degreeC. There were no oral and genital lesions. No psoriasis. The drugs used during the present and previous admissions were reviewed. Previous admission (04/04-22/ 20): Linezolid, ciprofloxacin, meropenem 04/13-22, piperacillin/tazobactam, hydroxychloroquine, azithromycin, ceftriaxone. Upon discharge amoxicillin/acid clavulanic. Present admission (04/25) Cutaneous reaction 04/28. 04/25: meropenem, paracetamol, enoxaparin, insulin, omeprazole, venlafaxine. 04/26: Darbepoetin, furosemide, mycophenolate in single dose. 04/27: Linezolid, macrogol, Clopidogrel, Magnesium, Calcitriol. Medical records: DM type 2, liver transplantation due to HCV cirrhosis, HCV recurrence, uninodular hepatocarcinoma, advanced CKD, secondary hyperparathyroidism, multiple neurological antecedents. We performed a detailed study. We hypothesized with a pharmagological/ drug reaction with several drugs possibly involved and our main suspicion was an allergic reaction to beta-lactams. Biopsy: Subcorneal pustules, basal spongiosis and presence in the superficial dermis of edema and an inflammatory infiltrate with abundant neutrophils. No fungi. Findings compatible with clinical diagnosis of generalized acute exanthematic pustulosis (PEGA). Immunohistochemical study Covid19. (Jimenez Diaz Foundation) Finely granular positivity in endothelium and more coarse in sweaty epithelium. Neutrophilic superficial inflammatory component with presumably spure staining. ACe-2 (positive external control) is not detected. The patient presents a EuroSCAR score of 9, sum of the clinic and the pathological anatomy, and therefore defined diagnosis. Clinical diagnosis: PEGA secondary to meropenem. Conclusion(s): We present the case of a PEGA by meropenem, not very often described in the literature. We highlight the importance of differential diagnosis with viral infections. Skin tests, especially epicutaneous tests, are key to the diagnosis. (Figure Presented).

Calcitriol modifies tight junctions, improves barrier function, and reduces TNF-α-induced barrier leak in the human lung-derived epithelial cell culture model, 16HBE 14o.

Using the 16HBE 14o- human airway epithelial cell culture model, calcitriol (Vitamin D) was shown to improve barrier function by two independent metrics - increased transepithelial electrical resistance (TER) and reduced transepithelial diffusion of 14 C-D-mannitol (Jm ). Both effects were concentration dependent and active out to 168 h post-treatment. Barrier improvement associated with changes in the abundance of specific tight junctional (TJ) proteins in detergent-soluble fractions, most notably decreased claudin-2. TNF-α-induced compromise of barrier function could be attenuated by calcitriol with a concentration dependence similar to that observed for improvement of control barrier function. TNF-α-induced increases in claudin-2 were partially reversed by calcitriol. The ERK 1,2 inhibitor, U0126, itself improved 16HBE barrier function indicating MAPK pathway regulation of 16HBE barrier function. Calcitriol's action was additive to the effect of U0126 in reducing TNF- α -induced barrier compromise, suggesting that calcitriol may be acting through a non-ERK pathway in its blunting of TNF- α - induced barrier compromise. This was supported by calcitriol being without effect on pERK levels elevated by the action of TNF-α. Lack of effect of TNF- α on the death marker, caspase-3, and the inability of calcitriol to decrease the elevated LC3B II level caused by TNF-α, suggest that calcitriol's barrier improvement does not involve a cell death pathway. Calcitriol's improvement of control barrier function was not additive to barrier improvement induced by retinoic acid (Vitamin A). Calcitriol improvement and protection of airway barrier function could in part explain Vitamin D's reported clinical efficacy in COVID-19 and other airway diseases.

Evidence That Increasing Serum 25(OH)D Concentrations to 30 ng/mL in the Kingdom of Saudi Arabia and the United Arab Emirates Could Greatly Improve Health Outcomes.

Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer's disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart disease and stroke), type 2 diabetes, hypertension, chronic kidney disease, stroke, and infectious diseases such as acute respiratory tract diseases, COVID-19, influenza, and pneumonia, as well as adverse pregnancy outcomes. The respective evidence is based on ecological and observational studies, randomized controlled trials, mechanistic studies, and Mendelian randomization studies. However, randomized controlled trials on vitamin D supplementation have largely failed to show benefits, probably due to poor design and analysis. In this work, we aim to use the best available evidence on the potential beneficial effects of vitamin D to estimate the expected reduction in incidence and mortality rates of vitamin D-related diseases in the Kingdom of Saudi Arabia and the United Arab Emirates if minimum serum 25(OH)D concentrations were to be raised to 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% for stroke incidence, 20 to 35% for cardiovascular disease mortality, and 35% for cancer mortality rates depicted a promising potential for raising serum 25(OH)D. Methods to increase serum 25(OH)D concentrations at the population level could include food fortification with vitamin D3, vitamin D supplementation, improved dietary vitamin D intake, and sensible sun exposure.

Ascorbic Acid vs Calcitriol in Influencing Monocyte Chemoattractant Protein-1, Nitric Oxide, Superoxide Dismutase, as Markers of Endothelial Dysfunction: In Vivo Study in Atherosclerosis Rat Model.

Introduction: Ascorbic acid and calcitriol were frequently utilized in conjunction as therapy during the COVID-19 pandemic, and individuals with minor symptoms had notable improvements. There have been a few studies, often with conflicting findings, that examine the use of them for endothelium restoration and numerous clinical trial studies that failed to establish the efficacy. The aim of this study was to find the efficacy of ascorbic acid compared to calcitriol on the inflammatory markers monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO), and superoxide dismutase (SOD), as protective agents which play an important role in the early stages of atherosclerosis formation. This study was an experimental in vivo study. Methods: The total of 24 male Rattus norvegicus strain Wistar rats were divided into 4 groups, namely: control/normal group (N), atherosclerosis group (DL) given atherogenic diet, atherosclerosis group given atherogenic diet and ascorbic acid (DLC), and atherosclerosis group given atherogenic diet and calcitriol (DLD) treatment for 30 days. Results: Ascorbic acid and calcitriol treatment was significantly effective (P<0.05) in lowering expression of MCP-1 and increasing NO and SOD level. Calcitriol was superior to ascorbic acid in increasing SOD (P<0.05). There was no significant difference between ascorbic acid and calcitriol in decreasing MCP-1 and increasing NO (P>0.05). Discussion: Both treatments could reduce MCP-1, and increase NO and SOD by increasing antioxidants. In this study calcitriol was superior to ascorbic acid in increasing SOD, but not NO and decreasing MCP-1. According to the theory, it was found that calcitriol through nuclear factor erythroid 2-related factor 2 (Nrf2) causes a direct increase in the amount of SOD. Nrf2 is an emerging regulator of cellular resistance to oxidants. Conclusion: Ascorbic acid and calcitriol treatment was able to reduce MCP-1 and increase NO and SOD in atherosclerosis rat. Calcitriol was significantly superior in increasing SOD levels compared to ascorbic acid.

Role of vitamin D3 in selected pulmonary diseases with particular emphasis on lung fibrosis.

INTRODUCTION AND OBJECTIVE: For many years vitamin D3 was known only as a regulator of the calcium-phosphate and water-electrolyte balances. Recent studies have paid special attention to other biological effects of calcitriol (the bioactive form of vitamin D3) with particular emphasis on its influence on immune function. Thus, any alterations, especially deficiencies, in the physiological level of calcitriol have serious health consequences. The aim of the study was to summarise the current state of knowledge concerning the role of vitamin D3 in selected pulmonary diseases. REVIEW METHODS: The review was based on data obtained from articles published in PubMed between 2000-2022. Papers were reviewed for scientific merit and relevance. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: In the reviewed literature, much attention was paid to clinical studies focused on the role of vitamin D3 in the pathogenesis of selected respiratory diseases. As revealed in research over the last two decades, vitamin D3 deficiency increases the risk and worsens the course of asthma, cystic fibrosis, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, as well as COVID-19. Surprisingly, vitamin D supplementation has not always proved to be an effective therapeutic strategy. The review also presents the unique concept of the possibility of using vitamin D3 in the prevention and treatment of pulmonary fibrosis in the course of hypersensitivity pneumonitis. SUMMARY: Due to the multiplicity and variety of factors that affect the metabolism of vitamin D3, effective counteracting, and even more eliminating the negative consequences of disorders in the level and activity of calcitriol in the respiratory tract, seems to be a breakneck action. On the other hand, only a deep understanding of the role of calcitriol in the pathogenesis of lung diseases provides the chance to develop an effective therapy.

Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants.

The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four drug compound libraries were interrogated for their antiviral activities against SARS-CoV-2. Here, we show that the drug screen has resulted in 121 promising anti-SARS-CoV-2 compounds, of which seven were further shortlisted for hit validation: citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate. In particular, the active form of vitamin D, calcitriol, exhibits strong potency against SARS-CoV-2 on cell-based assays and is shown to work by modulating the vitamin D receptor pathway to increase antimicrobial peptide cathelicidin expression. However, the weight, survival rate, physiological conditions, histological scoring, and virus titre between SARS-CoV-2 infected K18-hACE2 mice pre-treated or post-treated with calcitriol were negligible, indicating that the differential effects of calcitriol may be due to differences in vitamin D metabolism in mice and warrants future investigation using other animal models.

Vitamin D: sources, physiological role, biokinetics, deficiency, therapeutic use, toxicity, and overview of analytical methods for detection of vitamin D and its metabolites.

Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.

Research Trends of Vitamin D Metabolism Gene Polymorphisms Based on a Bibliometric Investigation.

Vitamin D requires activation to show its pharmacological effect. While most studies investigate the association between vitamin D and disease, only a few focus on the impact of vitamin D metabolism gene polymorphisms (vitDMGPs). This bibliometric study aims to provide an overview of current publications on vitDMGPs (CYP27B1, CYP24A1, CYP2R1, CYP27A1, CYP2R1, DHCR7/NADSYN1), compare them across countries, affiliations, and journals, and inspect keywords, co-citations, and citation bursts to identify trends in this research field. CiteSpace© (version 6.1.R3, Chaomei Chen), Bibliometrix© (R version 4.1.3 library, K-Synth Srl, University of Naples Federico II, Naples, Italy), VOSviewer© (version 1.6.1, Nees Jan van Eck and Ludo Waltman, Leiden University, Leiden, Netherlands) and Microsoft® Excel 365 (Microsoft, Redmond, Washington, USA) classified and summarized Web of Science articles from 1998 to November 2022. We analyzed 2496 articles and built a timeline of co-citations and a bibliometric keywords co-occurrence map. The annual growth rate of vitDMGPs publications was 18.68%, and their relative research interest and published papers were increasing. The United States of America leads vitDMGPs research. The University of California System attained the highest quality of vitDMGPs research, followed by the American National Institutes of Health and Harvard University. The three productive journals on vitDMGPs papers are J. Steroid. Biochem. Mol. Biol., PLOS ONE, and J. Clin. Endocrinol. Metab. We highlighted that the vitDMGPs domain is relatively new, and many novel research opportunities are available, especially those related to studying single nucleotide polymorphisms or markers in a specific gene in the vitamin D metabolism cycle and their association with disease. Genome-wide association studies, genetic variants of vitDMGPs, and vitamin D and its role in cancer risk were the most popular studies. CYP24A1 and CYB27A1 were the most-studied genes in vitDMGPs. Insulin was the longest-trending studied hormone associated with vitDMGPs. Trending topics in this field relate to bile acid metabolism, transcriptome and gene expression, biomarkers, single nucleotide polymorphism, and fibroblast growth factor 23. We also expect an increase in original research papers investigating the association between vitDMGPs and coronavirus disease 2019, hypercalcemia, Smith-Lemli-Opitz syndrome, 27-hydroxycholesterol, and mendelian randomization. These findings will provide the foundations for innovations in the diagnosis and treatment of a vast spectrum of conditions.

The Impact of Serum Levels of Vitamin D3 and Its Metabolites on the Prognosis and Disease Severity of COVID-19.

Vitamin D is among the increasingly consumed dietary supplements during the COVID-19 pandemic. It plays a regulatory role in the immune system and moderates the renin-angiotensin system, which is implicated in infection pathogenesis. However, the investigation of serum levels of vitamin D3 forms and their relative ratios in COVID-19 patients is worth investigation to understand the impacts of disease severity. Hence, we investigated the serum levels of vitamin D3 (cholecalciferol) and its metabolites (calcifediol and calcitriol), in addition to their relative ratios and correlations with angiotensin-converting enzyme 2 (ACE2), interleukin-6 (Il-6), and neutrophil-lymphocyte ratio (NLR) in COVID-19 patients compared with healthy controls. Oropharyngeal specimens were collected from the study subjects for polymerase chain reaction testing for COVID-19. Whole blood samples were obtained for blood count and NLR testing, and sera were used for the analysis of the levels of the vitamin and its metabolites, ACE2, and IL-6. We enrolled 103 patients and 50 controls. ACE2, Il-6, and NLR were significantly higher in the patients group (72.37 ± 18.67 vs. 32.36 ± 11.27 U/L, 95.84 ± 25.23 vs. 2.76 ± 0.62 pg/mL, and 1.61 ± 0.30 vs. 1.07 ± 0.16, respectively). Cholecalciferol, calcifediol, and calcitriol were significantly lower in patients (18.50 ± 5.36 vs. 29.13 ± 4.94 ng/mL, 14.60 ± 3.30 vs. 23.10 ± 3.02 ng/mL, and 42.90 ± 8.44 vs. 65.15 ± 7.11 pg/mL, respectively). However, their relative ratios were normal in both groups. Levels of the vitamin and metabolites were strongly positively, strongly negatively, and moderately negatively correlated with ACE2, Il-6, and NLR, respectively. COVID-19 infection severity is associated with a significant decrease in vitamin D3 and its metabolites in a parallel pattern, and with a significant increase in ACE2, Il-6, and NLR. Higher levels of vitamin D and its metabolites are potentially protective against severe infection.

Vitamin D Regulation of Immune Function.

PURPOSE OF REVIEW: To review the mechanisms by which vitamin D and its metabolites regulate the immune system to facilitate the ability of the body to prevent and/or treat SARS-CoV2 and other respiratory infections and encourage further research into the role that vitamin D supplementation plays in preventing/treating such infections. RECENT FINDINGS: Vitamin D deficiency is associated with an increased risk of SARS-CoV2 and other respiratory infections. Clinical trials in general demonstrate that correction of vitamin D deficiency reduces the risk of hospitalization, ICU admission, and death from SARS-CoV2 infection. The airway epithelium and alveolar macrophages express the enzyme, CYP27B1, that produces the active metabolite of vitamin D, 1,25(OH)2D, and the vitamin D receptor, VDR. Vitamin D and its metabolites promote the innate immune response, which provides the first line of defense against viral and bacterial infections while restricting the adaptive immune response, which if unchecked promotes the inflammatory response leading to the acute respiratory distress syndrome and death. The rationale for treating vitamin D deficiency to reduce the risk of SARS-CoV2 infection and supplementing patients with vitamin D early in the course of SARS-CoV2 infection rests primarily on the ability of vitamin D metabolites to promote an effective immune response to the infection.

Serum vitamin D levels and COVID-19 during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Serum vitamin D levels are reported to be associated with the risk of incidence and severity of COVID-19 in the general population. During pregnancy, immune system alterations in line with changes in vitamin D metabolism may affect the course of COVID-19. Thus, we aimed to systematically review the association between vitamin D, pregnancy, and COVID-19. METHODS: A systematic literature search was conducted in PubMed, Scopus, Web of Science, Embase, and Google Scholar until the end of May 2022. Mean differences (MD) with 95% CI were used as desired effect sizes to assess the association of serum vitamin D levels with the risk of incidence and severity of COVID-19 in pregnant women. RESULTS: Among 259 records, 7 and 6 studies were included in the systematic review and meta-analysis, respectively. All included studies had acceptable quality. Our results demonstrated an insignificant difference between infected women and non-infected controls (MD = -2.55 ng/ml, 95% CI: -6.85 - 1.74). But serum vitamin D levels in severe/moderate cases compared to mild ones (MD = -2.71 ng/ml, 95% CI: -4.18 to -1.24) are significantly lower. CONCLUSION: Based on the current evidence, serum vitamin D level does not associate with the risk of SARS-CoV-2 infection among pregnant women, but we find a significant association with the severity of the disease. These findings may be helpful in similar conditions and future studies to better understand the complex immune alterations during pregnancy.

Vitamin D as a drug: new therapeutic approaches

Vitamin D is one of the essential vitamins and has recently been demonstrated to be much more important for the appropriate functioning of the human body and well-being than initially believed. Although vitamin D is mainly known for its link with bone fractures and bone diseases, recent studies revealed that vitamin D and its analogues have revealed many pharmacological actions covering the regulation of cell growth, inhibition of inflammation, and improvement of neuromuscular function and immune function. Moreover, vitamin D and its analogues are reported to have role in different types of cancers, skin diseases, diabetes mellitus and infections caused by different bacterial and viral pathogens including SARS-CoV-2. The goal of this study is to evaluate the scientific literature on therapeutic uses of vitamin D and its analogues against different diseases and health condition. Special attention has been given to COVID-19 infection, cancer, skin diseases, and diabetes. The molecular mechanisms involved are also explored.

Management of COVID-19-A Review

Coronavirus disease-2019 (COVID-19) has gained much popularity not only in the Wuhan city of China but internationally also;in January 2020, the corona rapidly spread to many countries like the USA, Italy, Russia, India, Singapore, Pakistan, Thailand, Canada, Australia, England, and so on through passengers traveling to other countries. Corona patients can be cured with synthetic drugs, traditional herbal medicines (THM), use of Vitamin D and the quarantine approach. Different allopathic medicines, herbal extracts, and vitamin D have been observed to be useful in the treatment of novel coronavirus, like Remdesivir, hydroxychloroquine, Teicoplanin, Lopinavir+ Ritonavir, Ribavirin + corticosteroids, Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. Various antiviral drugs are used to treat COVID-19, alone or in combination with other medications like Interferon-α, Lopinavir + Ritonavir, Arbidol, corticosteroids, etc., and some herbal extracts;also quarantine approach and Vitamin D are used that not only cure the infection but also boost up our immunity. For this review article, different papers were searched on Google Scholar, Scopus, WHO’s website, PubMed, clinicaltrials.gov and other relevant scientific research websites. In this review article, we have discussed the current strategies that are being used to treat COVID-19. Along with allopathic drugs, some herbal extracts can also be used to treat this novel coronavirus, like Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. and even vitamin D.

Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol.

The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin-angiotensin-bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents.

Calcifediol for Use in Treatment of Respiratory Disease.

Calcifediol is the prohormone of the vitamin D endocrine system (VDES). It requires hydroxylation to move to 1,25(OH)2D3 or calcitriol, the active form that exerts its functions by activating the vitamin D receptor (VDR) that is expressed in many organs, including the lungs. Due to its rapid oral absorption and because it does not require first hepatic hydroxylation, it is a good option to replace the prevalent deficiency of vitamin D (25 hydroxyvitamin D; 25OHD), to which patients with respiratory pathologies are no strangers. Correcting 25OHD deficiency can decrease the risk of upper respiratory infections and thus improve asthma and COPD control. The same happens with other respiratory pathologies and, in particular, COVID-19. Calcifediol may be a good option for raising 25OHD serum levels quickly because the profile of inflammatory cytokines exhibited by patients with inflammatory respiratory diseases, such as asthma, COPD or COVID-19, can increase the degradation of the active metabolites of the VDES. The aim of this narrative revision is to report the current evidence on the role of calcifediol in main respiratory diseases. In conclusion, good 25OHD status may have beneficial effects on the clinical course of respiratory diseases, including COVID-19. This hypothesis should be confirmed in large, randomized trials. Otherwise, a rapid correction of 25(OH)D deficiency can be useful for patients with respiratory disease.

Network Pharmacology and Bioinformatics Analyses Identify Intersection Genes of Vitamin D3 and COVID-19 as Potential Therapeutic Targets.

Purpose: The persistent pandemic of coronavirus disease 2019 (COVID-19), the discovery of gastrointestinal transmission routes and the possible susceptibility of cancer patients to COVID-19 have forced us to search for effective pathways against stomach adenocarcinoma (STAD)/COVID-19. Vitamin D3 (VD3) is a steroid hormone with antiviral, anti-inflammatory and immunomodulatory properties. This study aimed to evaluate the possible functional role and potential mechanisms of action of VD3 as an anti-COVID-19 and anti- STAD. Methods: Clinicopathological analysis, enrichment analysis and protein interaction analysis using bioinformatics and network pharmacology methods. Validate the binding activity of VD3 to core pharmacological targets and viral crystal structures using molecular docking. Results: We revealed the clinical characteristics of STAD/COVID-19 patients. We also demonstrated that VD3 may be anti- STAD/COVID-19 through antiviral, anti-inflammatory, and immunomodulatory pathways. Molecular docking results showed that VD3 binds well to the relevant targets of COVID-19, including the spike RBD/ACE2 complex and main protease (Mpro, also known as 3CLpro). We also identified five core pharmacological targets of VD3 in anti-STAD/COVID-19 and validated the binding activity of VD3 to PAI1 by molecular docking. Conclusion: This study reveals for the first time that VD3 may act on disease target gene SERPINE1 through inflammatory and viral related signaling pathways and biological functions for the therapy of STAD/COVID-19. This may provide a new idea for the use of VD3 in the treatment of STAD/COVID-19.

Antiviral Activity of Vitamin D and COVID 19: Current Understanding

Innate and adaptive immune responses, which are intimately related to the evolution of many infectious diseases, are influenced by the biologically active form of vitamin D. From a mechanical perspective, there are several rationales to assume that vitamin D positively modifies host responses to SARS-CoV-2, either in the early infection or subsequent hyper-inflammatory stages of COVID-19. It has been long known that vitamin D metabolites induce antiviral effects through indirect and direct mechanisms via antimicrobial peptides, immune modulation, the interaction between major viral and cellular particles, initiation of apoptosis and autophagy, and diversity of hereditary and epigenetic aspects. The remarkable overlap between the deficiency of vitamin D and risk factors for severe COVID-19, including obesity, aging, and Black or Asian ethnicity, has motivated researchers to assume that supplementation of vitamin D can be promising as a preventive or treatment agent for COVID-19. Since the outset of the pandemic, researchers have integrated literature searches and cross-sectional statistical studies to appraise the vitamin D level impact of COVID-19, whereby nearly 30 observational studies have confirmed that the incidence, severity, and mortality of COVID-19 are inversely related to the serum 25OHD concentrations. Also, some recently announced clinical trials indicated that vitamin D supplementation has a positive effect on the severity of COVID-19;however, other studies, including clinical trials, have not supported that, especially if we take into account what was revealed in a recent clinical trial, i.e., airway diseases are related to the irregular metabolism of vitamin D increasing the potential of developing vitamin D deficiency due to pulmonary inflammation. Therefore, more dedicated studies are required without critical limitations to ascertain the actual effect of vitamin D in preventing and treating COVID-19, and if its effectiveness is proven, the effective dose must be determined. © 2021 Bentham Science Publishers. All rights reserved.

POS-252 THE DIFFERENTIAL IMPACT OF TWO NOVEL INTRAVENOUS IRON AGENTS ON FIBROBLAST GROWTH FACTOR 23, PHOSPHATE AND OTHER CLINICAL AND FUNCTIONAL MARKERS: METHODOLOGY AND BASELINE DATA

Introduction: Third generation intravenous (IV) iron preparations are increasingly used in the treatment of non-dialysis dependent chronic kidney disease (CKD) associated iron deficiency. Such compounds allow rapid delivery of large concentrations of iron safely at a single sitting. Evidence suggests that their use may lead to improved cardiovascular outcomes. Nonetheless, concerns exist regarding the potential induction of hypophosphatemia via fibroblast-growth-factor 23 (FGF-23) following the use of certain compounds. Raised FGF-23 has been associated with mineral bone and cardiac disorders, alongside prognostic implications. No prior study has provided a head-to-head comparison between iron preparations in CKD. This pilot study is designed to primarily investigate the differential impact of two different IV iron compounds on FGF-23 and phosphate in patients with CKD;secondarily we examine the impact of these compounds on bone markers and functional status, quality of life and cardiovascular function. Methods: This is a randomized controlled double-blinded pilot study recruiting patients with CKD stage 3a – 5 (non-dialysis) and iron deficiency +/- anemia. Patients are randomized to receive either ferric carboxymaltose or ferric derisomaltose over two infusions (one-month apart) to achieve full repletion. The initial dose administered is 1000 mg for both medications, with 500 mg or 1000 mg reserved for the second dose depending on weight and hematinics. Follow up is over a period of three months following the first infusion with measurements of intact FGF-23, phosphate, phosphaturia, vitamin D, parathyroid hormone, bone metabolism markers, functional status and quality of life and cardiac markers (figure 1). [Formula presented] Results: 168 patients were referred to the specialist renal anemia services for pre-screening. Ninety-nine were contacted for interest to participate, with 64 individuals declining to join. The commonest reason for not participating, was the COVID-19 pandemic (43.3%) with patients not keen to travel. Thirty-five patients were screened, and 27 patients enrolled in the study, of which 26 were randomized to receive iron (figure 2). One patient withdrew from the study, as they were unable to attend appointments following successful screening. In our baseline cohort the median age was 67.9 (12.4) and 17 participants were male. Mean hemoglobin was 100.3 (13.5) and hematinic markers consistent were consistent with iron deficiency. Median eGFR was 18.0 (11.3) ml/min/1.73 m2;the population as expected had a raised intact FGF-23 (212.1 (116.4) pg/ml). Serum calcium and phosphate were within normal parameters, while parathyroid hormone and 1,25 (OH)2 Vitamin D were deranged (Table 1). [Formula presented] [Formula presented] Conclusions: ExplorIRON-CKD, like a number of trials, experienced significant disruption in recruitment due to COVID-19. This study will provide further insight to the potential induction of FGF-23 following administration of specific intravenous iron compounds, and identify whether such a differential effect exists in patients with CKD. The effect of such induction in terms of phosphate and other markers of bone metabolism, functional status and cardiac functioning will be observed. The results will aid in hypothesis generation for further studies to identify the potential long-term impact of iatrogenic FGF-23 increase in patients with CKD. Conflict of interest Potential conflict of interest: This study received funding support from Pharmacosmos A/S and the Kidney Research Yorkshire Charity Fund. The funders had no role in the study design, data collection and analysis, and decision to publish or preparation of the . I have no potential conflicts of interest to disclose.