Vitamin D: A Potential Prophylactic and Therapeutic Agent against COVID-19

The COVID-19 pandemic caused by the novel SARS-CoV-2 is having a drastic and an unprecedented impact on public health and human life. In the spectrum of clinical symptoms, long-lasting residual effects and sheer number of fatalities, the Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1) or Middle East Respiratory Syndrome (MERS) epidemics that preceded it pale in comparison. The coronavirus of 2019, SARS-CoV-2, has infected approximately 3% of the world's population and killed about 2% of the infected. Studies indicate that 80% of COVID-19 patients in the West exhibit vitamin D deficiency and suffer from higher levels of inflammatory responses supporting a role for vitamin D status in COVID-19 risk. Vitamin D is active in many cells and tissues controlling an enormous number of genes, including those associated with infections, autoimmune diseases, and cancers. This vital micronutrient can enhance antioxidant production, raise cellular immunity, and dampen an overreactive immune response. It also exhibits immunomodulatory effects on angiotensin-converting enzyme 2 (ACE-2) receptors potentially rendering protective functions against acute lung injuries, including COVID-19 infection. Therefore, vitamin D's prophylactic and therapeutic roles against COVID-19 may be potent and medically advisable. However, there are also some articles that undermine its positive effect against COVID-19. In this chapter, I will examine the evidence supporting vitamin D's role in prophylaxis and therapeutic administration against SARS-CoV-2 infection and COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Serum vitamin D content in children with SARS-CoV-2 infection.

Aim of study. To study the total level of 25-hydroxyvitamin D in children with SARS-CoV-2 infection (COVID-19). Material and Methods. A total of 82 children aged 0-17 diagnosed with SARS-CoV-2 infection were enrolled. Depending on the severity of clinical symptoms, all children were divided into three groups according to the COVID-19 severity: asymptomatic, mild and moderate. The serum level of vitamin D in all patients was tested via the immunochemical method. Results. It was found that children with SARS-CoV-2 infection had lower serum level of vitamin D (29.92 [22.22;28.07] ng/ml) as compared with the control group (36.43 [32.05;44.08] ng/ml;p<0.001). A total of 90% of the children with SARS-CoV-2 infection were diagnosed with insufficiency or deficiency of vitamin D (<30 ng/ml). Only 10 % of the patients had normal levels of vitamin D. The insufficiency of vitamin D was found more often amongst children aged 0-11 and deficiency of total 25-hydroxyvitamin D was more common for children aged 12-17. The difference in serum levels of vitamin D depending on the severity of SARS-CoV-2 infection was not found. Male children with SARS-CoV-2 infection showed lower levels of vitamin D (p=0.013). Conclusion. A total of 90 % of the children with SARS-CoV-2 infection had insufficiency or deficiency of vitamin D regardless of the severity of clinical symptoms.Copyright © 2021, Krasnoyarsk State Medical University. All rights reserved.

RETROSPECTIVE STUDY OF VITAMIN D DEFICIENCY IN RHEUMATOLOGIC PATIENTS DURING THE COVID-19 PANDEMIC IN POLAND

BackgroundBefore the COVID-19 pandemic it was estimated that nearly 70% of the population is deficient in vitamin D - 25(OH)D <20ng/ml in Poland [1]. The percentage was expected to increase due to indoor isolation during the COVID-19 pandemic. Vitamin D has a positive effect on the condition of the bones, affects the course of autoimmune diseases, the course of neurological diseases, in type 2 diabetes, vitamin D supplementation improves glucose tolerance and reduces insulin resistance [2,3,4].ObjectivesThe aim of the retrospective study was to determine what percentage of rheumatology clinic patients suffer from vitamin D deficiency and whether this condition is effectively treated.MethodsIn January 2023, a retrospective analysis of the documentation of 172 patients treated at the Rheumatology Outpatient Clinic in Bełżyce (Poland) in 2022 was conducted.ResultsResults: The mean age of the 172 patients whose documentation was analyzed was 60.43 years (min 19, max 88). There were 132 women (76.8%) and 40 men (23.2%) in this group. The mean concentration of vitamin D was 25.57ng/ml±SD11.9 (min 5.7, max 75, Me 22.8). Vitamin D deficiency was found in 44% (serum concentration <20mg/ml), suboptimal concentration (20-30ng/ml) in 31%, optimal concentration (30-50ng/ml) in 21%, and high concentration (>50ng/ml) ml) in 4%. All those with a deficit or deficiency (75 people) were prescribed cholecalciferol in a dose of 20,000 units orally, 1 capsule twice a week after breakfast for 2 months [5]. Patients with optimal vitamin D levels were advised to take a dose of 2,000 units per day. Among the patients with deficit or deficiency, 48 people came for a follow-up visit to check the level of vitamin D (64% of the group with too low vitamin D concentration;28% of the entire group whose documentation was analyzed). In the follow-up examination, the mean concentration of vitamin D was 37.14±9.8ng/ml (min 28, max 84, Me 35.3). Therefore, a statistically significant increase in the concentration of vitamin D in the blood was noted (p<0.05). In the group of people who came for the follow-up examination, there were 35 women, whose mean age was 60.7 years and 13 men (mean age 68.2 years).Conclusion:1. During the COVID-19 pandemic in the group of outpatient rheumatology patients, 75% had a deficiency or suboptimal level of vitamin D.2. Treatment with cholecalciferol in a dose of 20,000 IU twice a week orally for 2 months is effective treatment of vitamin D deficiency.3. Too low percentage of patients diagnosed with vitamin D deficiency come for visits and check-ups.References[1]Hilger J., Friedel A., Herr R.. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2013;9: 1023.[2]Karczmarewicz E., Czekuć-Kryskiewicz E., Płudowski P. Effect of vitamin D status on pharmacological treatment efficiency-impact on cost- effective management in medicine. Dermatoendocrinology, 2013;5: 299-304.[3]Zhu J., Bing C., Wilding J.P.H. Vitamin d receptor ligands attenuate the inflammatory profile of IL-1β-stimulated human white preadipocytes via modulating the NF-κB and unfolded protein response pathways Biochemical and Biophysical Research Communications 2-18, 503: 1049-1056.[4]Luan W., Hammond L.A. Vuillermot S. Maternal vitamin d prevents abnormal dopaminergic development and function in a mouse model of prenatal immune activation. Scientific Reports 2018;8 (1) article numer 9741.[5]Płudowski P., Karczmarewicz E. i wsp. Witamina D: Rekomendacje dawkowania w populacji osób zdrowych oraz w grupach ryzyka deficytów.Wytyczne dla Europy Środkowej 2013 r. Standardy Medyczne/Pediatria 2013, 10, 573-578 (in Polish).Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Should Young Covid-19 Patients be Suplemented with Vitamin D?

It is well known that vitamin D's general immunomodulatory actions are helpful in viral infections and that a shortage is linked to a more serious prognosis for Covid-19. In this sistematic review, we examined the existing literature on evidence as to whether there is also link between vitamin D range levels in pediatric population and the outcome of the Covid-19 infection. We looked for studies that measured vitamin D blood concentrations and examined the effects of vitamin D supplementation in young infected patients. Vitamin D may decrease the risk of respiratory infections in a number of ways through its interactions with numerous cells, including by decreasing viral survival and replication, reducing the cytokine storm, raising angiotensin-converting enzyme 2 concentrations (ACE2) while not damaging the endothelial integrity. The incidence or severity of Covid-19 is linked with blood 25-hydroxyvitamin D concentrations, according to many observational studies. However experimental verification is still needed. Given their safety and broad therapeutic window, vitamin D supplements seem to be an effective way for individuals and doctors to prevent or treat Covid-19. Nonetheless, the outcomes of significant vitamin D randomized controlled trials are further needed.Copyright © 2022 Maria Nicolae et al., published by Sciendo.

A Retrospective Chart Review Evaluating Changes in 25-Hydroxyvitamin D Levels among Patients Attending the University Healthcare Centre during the COVID-19 Pandemic.

COVID-19-pandemic-related home confinement aids in limiting the spread of the virus but restricts exposure to sunlight, thereby possibly affecting 25(OH)D concentrations. This study aimed to investigate the effect of lockdown measures on 25(OH)D levels in outpatients visiting the healthcare centre over a period of two years. In this retrospective chart review, outpatients who visited a university healthcare centre for a health check-up over a period of two years were included. The patients' 25(OH)D serum levels and status were compared before, during, and after the lockdown periods. A total of 7234 patients were included in this study, with a mean age of 34.66 ± 16.78. The overall prevalence of 25(OH)D insufficiency, deficiency and sufficiency was 33.8%, 30.7% and 35.4%, respectively. The proportion of individuals with 25-(OH) D deficiency prior to lockdown was 29% and this proportion increased in the lockdown and post-lockdown periods to 31.1% and 32%, respectively. Although gender was less likely to have an impact on the 25 (OH) D level during the lockdown period (p = 0.630), we found an association between gender and 25 (OH) D status in the pre-lockdown and post-lockdown periods (p < 0.001 and p < 0.001, respectively). Another association between nationality and 25 (OH)D levels was found before, during and after the lockdown periods (p < 0.001). In addition, the youngest population, aged between 1 and 14, was strongly affected by the home confinement. Age had a positive and significant (p < 0.05) effect on 25 (OH) D status regardless of the different periods. Moreover, in the pre-lockdown period, male outpatients had 1.56 chance of having a sufficient level of 25 (OH)D. However, during the lockdown period, this chance decreased to 0.85 and then increased to 0.99 after the lockdown period. We found no statistically significant difference in the mean serum concentrations or in the prevalence of vitamin D insufficiency when we compared values from before, during and immediately after the COVID-19 lockdown period. However, there was a generally increased prevalence of vitamin D insufficiency in our study population. Another association between gender, nationality and age groups with 25(OH) D was found. Regular exposure to UVR is recommended for maintaining adequate vitamin D levels and to prevent vitamin D deficiency. Further research is needed to determine the best indications for vitamin D supplementation if confinement periods are extended and to consider the potential health consequences of prolonged confinement periods not only on vitamin D status but also on overall public health. The findings of this study may be considered by stakeholders for a targeted supplementation approach for risk groups.

Micronutrients Deficiency in Patients Receiving Parenteral Nutrition: Effect of Multivitamin Supply Shortage

Background: Total parenteral nutrition (TPN) is a life-saving therapy for patients with chronic intestinal failure. TPN typically consists of macronutrients (amino acids, dextrose, and lipids) as well as micronutrients (multi-vitamins [MVI] and trace elements) to meet fluid, calorie, and micronutrient needs. With the early years of PN administration, multiple deficiencies were noted leading to guidelines regarding need for daily use of essential trace element and MVI preparation for parenteral use. Unfortunately, during the last few years we have seen multiple shortages of PN related supplies including the most recent shortage of parenteral MVI preparation. Major organizations such as ASPEN have developed recommendations regarding management of shortages, however their clinical impact has not been fully evaluated. The current study evaluated the impact of MVI shortage on change in clinical practice and the prevalence of deficiency. Method(s): A retrospective review of electronic medical records for patients who received TPN during time of shortage in IV multivitamins supply due to COVID-19 crisis between January 2021 and June 2021. In our program, the shortage affected one TPN supplier. We included patients who received their TPN from affected supplier and who were tested for micronutrients including Vitamins A, B12, C, and D in the 6 months preceding the shortage in supply (period 1) as well as during the shortage period (period 2). Period 1 was defined as from July 1, 2020, to December 31, 2020, and period 2 was defined as from January 1, 2021, to June 30, 2021. In addition to baseline clinical characteristics, we captured changes in studied micronutrients. Result(s): Current retrospective analysis of a prospectively maintained database noted 21 patients (mean age of 63.3 +/- 13.8, 62% female) were impacted by MVI shortage during study period (Table 1). Most common primary diagnosis was Crohn's disease (33.3%) followed by enterocutaneous fistula (19%), and gastrointestinal dysmotility (14.3%). In 19/21 (90%) patients, MVI was administered 3 days per week in PN. In the remaining two patients who had short bowel,MVI was continued 7 days per week. Additionally, 19/21 (90%) patients also were supplemented orally with Vitamin D (17/21), Vitamin B12 (5/21), MVI (3/21), Vitamin C (1/21). There was a decline in average Vitamin C levels between the two study periods (Table 2) with a trend towards a decline in average 25-hydroxy vitamin D levels, while mean vitamin A and B12 levels did not change significantly. There was a significant increase in Vitamin D and C deficiencies, while no increase in deficiencies in Vitamin E, A, and B12 levels was noted (Figure 1). Conclusion(s): Unfortunately, shortages of key PN related supplies have become commonplace in the last few years. The most recent shortage affected MVI supplies. Our group managed the shortage through a combination of reduction of parenteral MVI administration to 3 days per week along with additional supplementation of specific micronutrients orally. Although with this strategy, there was an increase in Vitamin D and C levels falling below reference range, no significant deficiencies were noted. (Table Presented).

Vitamin D: Physiology, clinical applications, dietary sources, and requirements

Vitamin D, the sunshine vitamin, is essential for bone health and reducing risk of acute and chronic diseases, including autoimmune diseases, cancers, heart disease, type II diabetes, neurocognitive dysfunction and infectious diseases including COVID-19. Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Vitamin D status is determined by measuring 25-hydroxyvitamin D in the blood. To maintain a normal level of at least 30ngmL−1 (75nmolL−1) as recommended by the Endocrine Society Guidelines on Vitamin D, infants up to 1 year need 400–1000IUs, children 600IU–1000IU, adults 1500–2000IU of vitamin D daily. Obese adults require 2–3 times more vitamin D to satisfy their requirement because of the vitamin D being diluted in the body fat and not available. This can be accomplished by receiving sensible sun exposure in combination with ingesting foods that either naturally contain or are fortified with vitamin D along with a vitamin D supplement. © 2023 Elsevier Ltd. All rights reserved

Association of Vitamin D and Secondary Infection in COVID-19.

Introduction: Vitamin D plays a role in the modulation of cytokine release, inflammation, innate and adaptive immunity. It has been frequently discussed that the hyperinflammatory response that causes acute respiratory distress syndrome or other organ damage due to SARS-CoV-2 at the beginning of the pandemic can be modulated by the adequacy of vitamin D. The relationship of vitamin D with many conditions such as mortality, number of intensive care unit stays, disease severity, and organ damage has been investigated, but the information on its effect on secondary infections that occur during the course of the disease is limited. In this study, it was aimed to reveal the relationship of vitamin D with secondary infections that occur during the course of COVID-19 disease. Material(s) and Method(s): Medical records of patients hospitalized in the COVID-19 pandemic service with the diagnosis of COVID-19 were evaluated retrospectively. Result(s): One hundred eighty-one patients were included in the study. The mean of 25(OH) vitamin D was found to be 18.76 +/- 9.82 ng/mL. When 25-hydroxy vitamin D was compared with gender, disease severity, mortality, need for mechanical ventilation and presence of symptoms, no statistically significant difference was found (p> 0.05). The medical data of the patients during their hospitalization were analyzed and secondary infection was detected in 14.9% (n= 27). When 25-hydroxy vitamin D and the presence of secondary infection were compared, the 25(OH)D vitamin level of those with secondary infection was found to be low and this was found to be statistically significant (p= 0.016). As a result of the evaluation made by ROC analysis, 25-hydroxy vitamin D was found to have a diagnostic value in predicting positive culture results in COVID-19 patients (AUC= 0.771, 95% Confidence Interval= 0.612-0.810, p= 0.003, p< 0.05). Conclusion(s): While vitamin D continues to be an important topic of discussion in COVID-19 disease due to its effects on the immune system, it should not be forgotten that low vitamin D increases the risk of secondary infection developing in the course of COVID-19 and this may have an impact on prognosis.Copyright © 2022 Bilimsel Tip Yayinevi. All rights reserved.

IDF2022-0635 Can COVID-19 infection provoke new-onset A-beta+ KPD (ketosis-prone diabetes)? - Insights from an Indian prospective study

Background COVID-19 as a trigger for A-beta+ ketosis-prone diabetes (KPD) [1,2] in previously normoglycemic individuals presenting with new-onset DKA, has been sparsely studied. Aim To study prospective changes in insulin secretion and insulin resistance in suspected A-beta+ KPD patients presenting with COVID-associated new-onset DKA. Method 22 previously non-diabetic, antibody-negative patients with new-onset DKA and RT-PCR positive COVID-19 (suspected A-beta + KPD), were followed up for one year. They were compared with 20 Type 1A and 18 Type 2 DM patients, with serial assessments (0,6 and 12 months) of insulin secretion rates (ISR) and multi-tissue insulin resistance (IR). 75-g OGTT with serial glucose, insulin and C-peptide estimation (0,15, 30,45, 60,90,120, 150 and 180 minutes) was used to derive IS, while hepatic and peripheral IR was calculated based on study by Ghani et al. [3]. Results At baseline, ISR in suspected KPD (n = 22) was significantly reduced but similar to Type 1A DM(p = 0.15). Serial ISR demonstrated complete recovery in 17 (77%) patients who became insulin independent at one-year follow-up (remission), while 5(23%) patients continued to require insulin (non-remission). KPD patients showed significant hepatic and peripheral IR at baseline compared to Type 1A DM (p < 0.05). The remission group (n = 17) showed significantly enhanced recovery of hepatic and peripheral insulin sensitivity at 6 and 12 months follow-up (all p < 0.01) compared to the non-remission (n = 5) group, with IR in the latter being comparable to Type 2 DM at follow-up (all p > 0.05). Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were factors associated with poorer recovery of beta-cell secretion amongst the KPD patients. Conclusion This is the first prospective study to demonstrate progressive recovery of p-cell secretion in new-onset A-beta + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM.Copyright © 2023 Elsevier B.V.

Role of vitamin D in modulating the immune response to SARS-CoV-2 and other coronavirus infections.

In recent years, new data have been obtained on the significant prevalence of vitamin D (VD) deficiency in the population, and knowledge about the role of vitamin D in the regulation of many physiological processes in the body, including the functioning of the immune system, has increased. The SARS-CoV-2 pandemic has further highlighted the issue of an adequate immune response in vitamin D deficiency. Objective of the review. To present and summarize the evidence on the role of VD in different parts of the immune response in COVID-19, to analyze available studies of the VD status effect on the course and outcome of COVID-19 in patients from different population groups. Material and methods. A search of domestic and foreign literature on the role of VD in the immune response in respiratory viral infections and SARS-CoV-2, as well as practical measures of VD-status correction in COVID-19, was performed. We used Scopus, Web of Science, PubMed, Google Scholar, eLibrary, and Cyberleninka databases. Results. Numerous clinical and observational studies have found an association between 25-hydroxyvitamin D levels, COVID-19 severity, and mortality. This association can be explained by the multifaceted role of vitamin D in the physiology of the human immune and endocrine systems. On the immunological side, the active form of VD promotes the secretion of antimicrobial peptides responsible for inhibiting viral replication and stimulates autophagy by increasing the level of Beclin1 protein and decreasing the level of mTOR protein regulating cellular homeostasis. It leads to the presentation of antigens followed by activation of the antiviral pathway of type I interferons. VD also stabilizes intercellular junctions, including those in the airway epithelium, reducing their permeability to pathogens, stimulates the activity of angiotensin-converting enzyme-2, whose receptors are a conduit for SARS-CoV-2 into cells, and several pathophysiological responses associated with the disease symptoms and acute lung injury. Adequate vitamin D status can provide significant benefits during the pandemic. Conclusion. To date, ideas about the role of vitamin D in regulating the immune response in respiratory infections have significantly expanded. However, its use in the complex preventive measures and adjuvant therapy of viral infections, including COVID-19, should be the subject of further scientific research.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

The relationship between dialysis adequacy and COVID-19 onset and mortality risk: Single center experience

Aim: We primarily aimed in this study was to evaluate risk factors for COVID-19 infection and if any association between dialysis inadequacy in COVID-19 infection in maintenance hemodialysis (MHD) patients. Secondly aimed to describe prevalence and risk factors associated with long-lasting symptoms of non-deceased COVID-19 MHD patients before vaccination. Material(s) and Method(s): One hundred one MHD patients infected with COVID-19 and 100 MHD patients without the infection were enrolled in this retrospective cross-sectional study. Risk factors for mortality, need to intensive care unit (ICU) stay and long-lasting symptoms were analyzed. Result(s): The mean age of patients was 59.13+/-13.58 years. COVID-19 infected patients had significantly higher number of patients with DM, COPD, CHF. The need for ICU was found to be statistically significantly higher in patients with COPD and DM. In our results, the patients who had lower Kt/V at admission hospital had more than 5 fold higher rate of COVID-19 those have higher Kt/V. We analyzed risk factors for mortality at, one year included higher age, higher CRP and lower base-line Kt/V were diagnostic criteria. Older MHD patients had a high frequent of long-lasting symptoms. Low Kt/V, low hemoglobin level and high CRP level associated with a higher risk of long-lasting symptoms (p=0.00, p=0.001, p=0.02) Discussion: We conclude that DM, CHF, COPD, older age, obesity were poor prognostic factors for in infected with COVID-19. Dialysis adequacy parameters of Kt/V, serum albumin level, hemoglobin level were significantly lower in need to ICU and deceased patients.Copyright © 2023, Derman Medical Publishing. All rights reserved.

Vitamin D and COVID-19: where are we now?

The pandemic caused by the SARS-CoV-2 virus has triggered great interest in the search for the pathophysiological mechanisms of COVID-19 and its associated hyperinflammatory state. The presence of prognostic factors such as diabetes, cardiovascular disease, hypertension, obesity, and age influence the expression of the disease's clinical severity. Other elements, such as 25-hydroxyvitamin D (25(OH)D3) concentrations, are currently being studied. Various studies, mostly observational, have sought to demonstrate whether there is truly a relationship between 25(OH)D3 levels and the acquisition and/or severity of the disease. The objective of this study was to carry out a review of the current data that associate vitamin D status with the acquisition, evolution, and/or severity of infection by the SARS-CoV-2 virus and to assess whether prevention through vitamin D supplementation can prevent infection and/or improve the evolution once acquired. Vitamin D system has an immunomodulatory function and plays a significant role in various bacterial and viral infections. The immune function of vitamin D is explained in part by the presence of its receptor (VDR) and its activating enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1) in immune cells. The vitamin D, VDR, and Retinoid X Receptor complex allows the transcription of genes with antimicrobial activities, such as cathelicidins and defensins. COVID-19 characteristically presents a marked hyperimmune state, with the release of proinflammatory cytokines such as IL-6, TNF-α, and IL-1ß. Thus, there are biological factors linking vitamin D to the cytokine storm, which can herald some of the most severe consequences of COVID-19, such as acute respiratory distress syndrome. Hypovitaminosis D is widespread worldwide, so the prevention of COVID-19 through vitamin D supplementation is being considered as a possible therapeutic strategy easy to implement. However, more-quality studies and well-designed randomized clinical trials are needed to address this relevant question.

Is serum 25-hydroxyvitamin D levels associated with severity of COVID-19 disease? A retrospective study

Background: COVID-19 still needs to be further investigated for risk and preventing factors. Various factors are known to negatively affect the course of disease in patients suffering from COVID-19. As it is known, vitamin D affects the immune system and a vitamin D deficiency is often seen in patients with ARDS. Thus, we hypothesize that vitamin D could be one of those influencing factors. However, an association between the vitamin D level and the severity of the disease remains unclear. Aim(s): This study aims to contribute to the clarification whether there is a correlation between the serum 25- hydroxyvitamin D level and the severity of COVID-19 disease in hospitalized SARS-CoV-2 positive patients. Method(s): This is a retrospective, observational study in a single-center setting in Switzerland. Data of approximately 1200 hospitalized patients between January 2020 and December 2021 with an available and current 25- hydroxyvitamin D value and a SARS-CoV-2 positive immune status will be analysed. Quantitative and descriptive statistics as well as multivariable regression are used to assess the relationships between the serum 25- hydroxyvitamin D level and the severity of COVID-19 disease, adjusted for known confounding variables of vitamin D deficiency and COVID-19 severity such as age, sex and comorbidities. Result(s): As the study is ongoing, no results are available yet, but will be by the time of the congress. Conclusion(s): The results of this study may contribute to new treatment and prevention methods of COVID-19 together with more evidence from clinical trials to assess the causality of the relationship between vitamin D level and the severity of COVID-19 disease.

Vitamin D: immune function, inflammation, infections and auto-immunity.

Vitamin D plays an active role beyond mineral metabolism and skeletal health, including regulation of the immune system. Vitamin D deficiency is widely prevalent, and observational studies link low vitamin D status to a risk of infections and auto-immune disorders. Reports indicate an inverse relationship between vitamin D status and such conditions. This review details vitamin D signalling interactions with the immune system and provides experimental and clinical evidence evaluating vitamin D status, vitamin D supplementation and host susceptibility to infections, inflammation and auto-immunity. The published literature including related reviews, systematic reviews, meta-analyses, randomised controlled trials (RCTs), observational studies and basic science reports have been synthesised. Meta-analyses of observational studies have demonstrated a link between low vitamin D status and risk of acute respiratory infections, COVID-19 disorders, multiple sclerosis, type 1 diabetes (T1DM), inflammatory bowel disease (IBD), systemic lupus erythematosus and other auto-immune disorders. Observational studies suggest that vitamin D supplementation may protect against several infectious and auto-immune conditions. Meta-analyses of RCTs had mixed results, demonstrating a small protective role for vitamin D supplementation against acute respiratory infections, especially in those with vitamin D deficiency and children, and providing modest benefits for the management of T1DM and IBD. Vitamin D status is inversely associated with the incidence of several infectious and auto-immune conditions. Supplementation is recommended for those with vitamin D deficiency or at high risk of deficiency, and it might provide additional benefit in acute respiratory infections and certain auto-immune conditions.

Vitamin D Deficiency Prevalence in Hospitalized Patients with COVID-19 Significantly Decreased during the Pandemic in Slovakia from 2020 to 2022 Which Was Associated with Decreasing Mortality.

The coronavirus disease 2019 (COVID-19) pandemic has led to changes in lifestyle, which could influence vitamin D status on a population level. The purpose of our study was to compare 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized because of severe COVID-19 during two waves of the pandemic (2020/21 vs. 2021/22). A total of 101 patients from the 2021/22 wave were compared with 101 sex- and age-matched subjects from the 2020/21 wave. Patients from both groups were hospitalized during the winter season from 1 December to 28 February. Men and women were analyzed together and separately. The mean 25(OH)D concentration increased from 17.8 ± 9.7 ng/mL to 25.2 ± 12.6 ng/mL between waves. The prevalence of vitamin D deficiency (<20 ng/mL) decreased from 82% to 54%. The prevalence of adequate serum 25(OH)D concentration (>30 ng/mL) increased from 10% to 34% (p < 0.0001). The proportion of patients with a history of vitamin D supplementation increased from 18% to 44% (p < 0.0001). Low serum 25(OH)D concentration was independently associated with mortality after adjusting for age and sex for the whole cohort of patients (p < 0.0001). The prevalence of inadequate vitamin D status in hospitalized patients with COVID-19 in Slovakia decreased significantly, probably due to a higher rate of vitamin D supplementation during the COVID-19 pandemic.

Is the vitamin D status of patients with COVID-19 associated with reduced mortality? A systematic review and meta-analysis.

To conduct a systematic review and meta-analysis of studies assessing the association between serum vitamin D status and mortality in patients with COVID- 19. We searched PubMed and Embase for studies addressing the association of serum vitamin D levels and COVID-19 mortality published until April 24, 2022. Risk ratios (RRs) and 95% confidence interval (CIs) were pooled using fixed or random effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. The meta-analysis included 21 studies that measured serum vitamin D levels close to the date of admission, of which 2 were case-control and 19 were cohort studies. Vitamin D deficiency was associated with COVID-19 mortality in the overall analysis but not when the analysis was adjusted to vitamin D cutoff levels < 10 or < 12 ng/mL (RR 1.60, 95% CI 0.93-2.27, I2 60.2%). Similarly, analyses including only studies that adjusted measures of effect for confounders showed no association between vitamin D status and death. However, when the analysis included studies without adjustments for confounding factors, the RR was 1.51 (95% CI 1.28-1.74, I2 0.0%), suggesting that confounders may have led to many observational studies incorrectly estimating the association between vitamin D status and mortality in patients with COVID-19. Deficient vitamin D levels were not associated with increased mortality rate in patients with COVID-19 when the analysis included studies with adjustments for confounders. Randomized clinical trials are needed to assess this association.

Clinical Diagnostic Value of Serum 25-Hydroxyvitamin D in Severe Fever with Thrombocytopenia Syndrome.

Purpose: Severe Fever with Thrombocytopenia Syndrome (SFTS) is an infectious disease with rapid onset and high case fatality rate. The study was to explore the clinical value by examining the serum level of 25-hydroxyvitamin D (25 (OH) D) in SFTS patients. Methods: One hundred and five patients and 156 healthy controls were included. Univariate and multivariate regression analyses were performed to identify independent risk factors for disease progression. Subject operating characteristics (ROC) curves were drawn, and the corresponding area under the curve (AUC) was calculated to assess the sensitivity and specificity of the diagnostic disease. Results: The 25 (OH) D level of disease group was lower than that of healthy control group (22.12 (18.43, 25.86) ng/mL vs 27.36 (23.20, 32.71) ng/mL; P<0.05). The 25 (OH) D level of severe disease group was lower than that of mild disease group (20.55(16.30, 24.44) ng/mL vs 24.94(20.89, 31.91) ng/mL; P<0.05). And there was no significant difference of 25 (OH) D level between the survival group and death group in severe disease group. Multivariate Logistic regression analysis showed that the 25 (OH) D level under 19.665 ng/mL was an independent risk factor for the development of SFTS (OR = 0.901, P=0.040). Furthermore, age more than 68.5 years old and lactate dehydrogenase (LDH) more than 1023.5U/L were independent risk factors for death in severe patients with SFTS. Conclusion: Patients with SFTS have reduced 25 (OH) D level, and 25 (OH) D is a risk factor for disease severity in patients with SFTS. Vitamin D supplementation may be an effective measure to reduce the risk of infection and improve the prognosis.

Association of Vitamin D and Secondary Infection in COVID-19

Introduction: Vitamin D plays a role in the modulation of cytokine release, inflammation, innate and adaptive immunity. It has been frequently discussed that the hyperinflammatory response that causes acute respiratory distress syndrome or other organ damage due to SARS-CoV-2 at the beginning of the pandemic can be modulated by the adequacy of vitamin D. The relationship of vitamin D with many conditions such as mortality, number of intensive care unit stays, disease severity, and organ damage has been investigated, but the information on its effect on secondary infections that occur during the course of the disease is limited. In this study, it was aimed to reveal the relationship of vitamin D with secondary infections that occur during the course of COVID-19 disease. Materials and Methods: Medical records of patients hospitalized in the COVID-19 pandemic service with the diagnosis of COVID-19 were evaluated retrospectively. Results: One hundred eighty-one patients were included in the study. The mean of 25(OH) vitamin D was found to be 18.76 ± 9.82 ng/mL. When 25-hydroxy vitamin D was compared with gender, disease severity, mortality, need for mechanical ventilation and presence of symptoms, no statistically significant difference was found (p> 0.05). The medical data of the patients during their hospitalization were analyzed and secondary infection was detected in 14.9% (n= 27). When 25-hydroxy vitamin D and the presence of secondary infection were compared, the 25(OH)D vitamin level of those with secondary infection was found to be low and this was found to be statistically significant (p= 0.016). As a result of the evaluation made by ROC analysis, 25-hydroxy vitamin D was found to have a diagnostic value in predicting positive culture results in COVID-19 patients (AUC= 0.771, 95% Confidence Interval= 0.612-0.810, p= 0.003, p< 0.05). Conclusion: While vitamin D continues to be an important topic of discussion in COVID-19 disease due to its effects on the immune system, it should not be forgotten that low vitamin D increases the risk of secondary infection developing in the course of COVID-19 and this may have an impact on prognosis.

Role of vitamin D in modulating the immune response to SARS-CoV-2 and other coronavirus infections

In recent years, new data have been obtained on the significant prevalence of vitamin D (VD) deficiency in the population, and knowledge about the role of vitamin D in the regulation of many physiological processes in the body, including the functioning of the immune system, has increased. The SARS-CoV-2 pandemic has further highlighted the issue of an adequate immune response in vitamin D deficiency. Objective of the review. To present and summarize the evidence on the role of VD in different parts of the immune response in COVID-19, to analyze available studies of the VD status effect on the course and outcome of COVID-19 in patients from different population groups. Material and methods. A search of domestic and foreign literature on the role of VD in the immune response in respiratory viral infections and SARS-CoV-2, as well as practical measures of VD-status correction in COVID-19, was performed. We used Scopus, Web of Science, PubMed, Google Scholar, eLibrary, and Cyberleninka databases. Results. Numerous clinical and observational studies have found an association between 25-hydroxyvitamin D levels, COVID-19 severity, and mortality. This association can be explained by the multifaceted role of vitamin D in the physiology of the human immune and endocrine systems. On the immunological side, the active form of VD promotes the secretion of antimicrobial peptides responsible for inhibiting viral replication and stimulates autophagy by increasing the level of Beclin1 protein and decreasing the level of mTOR protein regulating cellular homeostasis. It leads to the presentation of antigens followed by activation of the antiviral pathway of type I interferons. VD also stabilizes intercellular junctions, including those in the airway epithelium, reducing their permeability to pathogens, stimulates the activity of angiotensin-converting enzyme-2, whose receptors are a conduit for SARS-CoV-2 into cells, and several pathophysiological responses associated with the disease symptoms and acute lung injury. Adequate vitamin D status can provide significant benefits during the pandemic. Conclusion. To date, ideas about the role of vitamin D in regulating the immune response in respiratory infections have significantly expanded. However, its use in the complex preventive measures and adjuvant therapy of viral infections, including COVID-19, should be the subject of further scientific research.