Correlation of serum YKL-40, 25(OH)D3 and HMGB1 expression levels with infection types and disease assessment in neonatal pneumonia

Objective: To investigate the serum levels of human cartilage glycoprotein 39 (YKL-40), 25-hydroxy vitamin D3 [25-hydroxy vitamin D3, 25 (OH)D3] and high mobility group protein B1 (high mobility group protein B1, HMGB1) level changes in the diagnosis of neonatal pneumonia infection type and the application of disease assessment. Methods: A total of 105 children with NP who were admitted to the Department of Neonatology, Longhua District People's Hospital of Shenzhen from January to December 2020 were selected as the research objects. According to different infectious pathogens, they were divided into a bacterial pneumonia group of 40 cases and a non-bacterial pneumonia group of 65 cases. According to the severity of the disease, they could be divided into 69 cases of mild pneumonia group and 36 cases of severe pneumonia group, and 85 healthy newborns were selected as the control group during the same period. Serum levels of YKL-40, 25 (OH)D3 and HMGB1 were detected by enzyme-linked immunosorbent assay. ROC curve was used to analyze the differential diagnosis value of YKL-40, 25 (OH) D3 and HMGB1 for NP alone or in combination. Spearman rank correlation was used the relationship between serum YKL-40, 25 (OH) D3 and HMGB1 levels and the severity of the disease in children with NP was analyzed. Results: The serum levels of YKL-40 (46.39 +or- 8.36 ng/ml, 40.28 +or- 8.47 ng/ml)and HMGB1 (23.38 +or- 5.66 ng/ml, 17.32 +or- 4.18 ng/ml) in the bacterial pneumonia groups and non-bacterial pneumonia groups were significantly higher than those in the control group (30.49 +or- 6.35 ng/ml, 12.56 +or- 3.22 ng/ml), and the differences were statistically significant (F=939.480, 99.507, all P < 0.05), while bacterial and non-bacterial pneumonia groups serum 25 (OH) D3 (12.76 +or- 3.57 g/L, 18.33 +or- 4.21 g/L) levels were significantly lower than those in the control group (19.76 +or- 4.87 g/L), and the difference was statistically significant (F=225.752, P < 0.05). The serum levels of YKL-40 (52.56 +or- 9.68 ng/ml) and HMGB1 (26.74 +or- 4.57 ng/ml) in the severe group were significantly higher than those in the mild group (16.63 +or- 5.32 ng/ml, 9.63 +or- 2.38 ng/ml) and the control group (11.63 +or- 3.32 ng/ml, 6.34 +or- 2.06 ng/ml), the differences were all statistical significance (F=265.331, 55.426, all P < 0.05), and serum 25 (OH) D3 (9.76 +or- 3.54 g/L, 31.16 +or- 5.01 g/L)levels in the severe and mild were significantly lower than control groups (35.16 +or- 5.88 g/L) (F=55.426, P < 0.05) . The results of Spearman rank correlation analysis showed that the disease severity was positively correlated with serum YKL-40 and HMGB1 levels (r=0.727, 0.210, all P < 0.05), but negatively correlated with 25 (OH) D3 levels (r= -0.566, P < 0.05). The results of ROC curve analysis showed that the combined detection of YKL-40, 25 (OH) D3 and HMGB1 had the highest efficacy in diagnosing NP, the AUC was 0.912 (95%CI: 0.864-0.932), the sensitivity and specificity were 96.34%, 85.72%, respectively. In the single detection of each index, the differences in AUC were statistically significant (Z=0.746, 2.843, 3.662, all P < 0.05). The combined detection of the three had the highest diagnostic efficiency in distinguishing neonatal bacterial pneumonia from non-bacterial pneumonia, and its AUC was 0.894 (95%CI: 0.832-0.941), the sensitivity and specificity were 97.26%, 80.66%, respectively. Which was higher than the single test of each index, and the difference in AUC was statistically significant (Z=1.573, 3.228, 2.689, all P < 0.05). Conclusion: Serum levels of YKL-40, 25 (OH) D3 and HMGB1 had important clinical value in diagnosis of NP infection types and in reflecting the severity of children's disease, the combined detection of the three has better clinical diagnostic performance.

Worldwide Interest in Vitamin D, Negative Effects on Kidneys, and Bone Density: Analysis of Google Trends Data

Background: Besides its role in calcium homeostasis and bone mineralization, vitamin D may also reduce the risk of cancer, cardiovascular and autoimmune diseases. Excessive vitamin D intake can lead to life-threatening hypercalcemia and toxicity, however. Here, we wanted to determine the relative search volume (RSV) of interest in vitamin D and its adverse biological effects (hypercalcemia, renal failure, kidney stones, bone density).Methods: We used data from Google Trends to assess changes in RSV trends across the world's regions. Data were extracted via the search terms "cholecalciferol", "ergocalciferol, "hypercalcemia", "acute renal failure", "kidney stones", and "bone density" from queries in English from 1 January 2004 to 1 October 2018 in the tool's related query database. Statistical analysis was performed using SPSS (R) 22.0 for Windows (IBM Inc., Armonk, NY, USA, 10504-1722).Results: There was a correlation between the RSV of cholecalciferol and ergocalciferol (Spearman's correlation) and the RSV of hypercalcemia, renal failure, kidney stones, and bone density. As measured by the change in RSV score, the trend for interest in kidney stones increased more rapidly than that for the other search terms. There was a positive correlation between the RSV score for cholecalciferol (or ergocalciferol) and renal failure and between the RSV score for cholecalciferol (or ergocalciferol) and kidney stones, whereas there was a negative correlation between cholecalciferol and hypercalcemia. The interest of ergocalciferol increased in parallel with the interest in bone density. The highest concentration of interest in cholecalciferol occurred in North America, Europe, India and Australia, whereas interest in ergocalciferol was greater in Central and South America, Spain, and Thailand. Interest in kidney stones was greater than cholecalciferol in North America, Brazil, India, and Australia, while interest in bone density was greater than cholecalciferol in North America, Brazil, Italy, Spain, South Africa, and Australia.Conclusions: In the pre-pandemic COVID-19 (COronaVIrus Disease 19) era, our preliminary results showed a positive correla-tion between global interest in cholecalciferol and kidney stones and renal failure, respectively. However, we found an unexpected negative correlation between global interest in cholecalciferol and hypercalcemia. Additionally, we found a positive correlation between global interest in ergocalciferol and bone density. These correlations can inform health interventions and education.

A Scoping Review of Vitamin D for Nonskeletal Health: A Framework for Evidence-based Clinical Practice.

BACKGROUND: Low serum 25-hydroxy-vitamin D [25(OH)D] levels are prevalent worldwide. Although the benefits of vitamin D supplementation have focused on skeletal disorders (eg, rickets, osteomalacia, osteoporosis), emerging evidence for nonskeletal health merits further discussion. PURPOSE: The purpose of this review was to critically examine the vitamin D supplementation literature pertaining to nonskeletal health to help guide clinicians. METHODS: A scoping review that included observational studies and randomized clinical trials (RCTs) was performed. Evidence from meta-analyses and individual RCTs are discussed, and controversies and future directions are considered. FINDINGS: 25(OH)D deficiency is a ubiquitous condition associated with multiple nonskeletal diseases, including cardiometabolic (heart disease, diabetes, and kidney disease), immune (HIV/AIDS and cancer), lung (from traditional chronic disorders to coronavirus disease 2019), and gut diseases. Vitamin D deficiency also affects health across the life span (children, pregnant, and elderly), mental illness, and reproduction in both men and women. In contrast, vitamin D supplementation does not necessarily improve major medical outcomes, even when low 25(OH)D levels are treated. Screening for 25(OH)D status remains an important practice, primarily for high-risk patients (eg, elderly, women with osteoporosis, people with low exposure to sunlight). It is reasonable to supplement with vitamin D to treat 25(OH)D deficiency, such that if beneficial nonskeletal health occurs, this may be considered as a coadjutant instead of the central tenet of the disease. Furthermore, optimizing dosing regimens is an important clinical consideration. IMPLICATIONS: Although 25(OH)D deficiency is prevalent in nonskeletal diseases, there is no uniform evidence that vitamin D supplementation improves major medical outcomes, even when low 25(OH)D levels are corrected. Findings from RCTs warrant caution due to possible selection bias. Overall, vitamin D supplementation must be guided by circulating levels as a reasonable medical practice to correct 25(OH)D deficiency.

Interaction between vitamin D deficiency and COVID-19

Coronavirus Disease 2019 (COVID-19) poses an enormous challenge to health care systems throughout the world, but it doesn't affect every individual to the same extent. There is great variability in disease outcomes. Therefore, identifying the main prognostic risk factors is of paramount importance. These include increased age, skin pigmentation, obesity, pre-existing illness, and vitamin D deficiency. Vitamin D is a molecule with established effectiveness against various upper respiratory infections. This is due to its pivotal role as modulator of the innate and adaptative immune system through different mechanisms. Moreover, vitamin D can regulate the renin-angiotensin system that is exploited by SARS-CoV-2 for entry into the host cells. Vitamin D supplementation is thus a therapeutic option to consider, especially since it has low toxicity, and there are few currently available drugs for COVID-19 treatment. In this review chapter, we engage an immunological lens to discuss potential mechanisms by which vitamin D signaling might regulate COVID-19 disease susceptibility, severity, and by consequence, mortality. Hence, a critical analysis of the clinical trials published to date has been undertaken to address the value of vitamin D supplementation. We also discuss, based on plausible immunological mechanisms, the relationship between vitamin D and Long-COVID, as well as its effect on SARS-CoV-2 vaccination responsiveness. © 2023 Elsevier Inc. All rights reserved.

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.

Possible Impact of Vitamin D Status and Supplementation on SARS-CoV-2 Infection Risk and COVID-19 Symptoms in a Cohort of Patients with Inflammatory Bowel Disease.

The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.

Cholecalciferol as part of complex therapy for acute COVID-19

During the pandemic of new coronavirus infection, the prevalence of moderate to severe vitamin D deficiency remains high, which is a factor worsening the course of COVID-19. According to some studies, cholecalciferol therapy, added to standard COVID-19 ther-apy, is associated with improving the course and prognosis of the disease. Objective. To evaluate the effect of cholecalciferol therapy at a dose of 100,000 IU on clinical and laboratory parameters in patients with moderate to severe COVID-19 admitted to an infectious hospital. Material and methods. An open single-center interventional study included 129 COVID-19 patients who were further randomized into two groups. Group 1 patients (n=65) received a total dose of 100,000 IU of cholecalciferol in addition to the standard COVID-19 therapy. Group 2 patients (n=64) received standard therapy only. Results. On day 9 of hospitalization, group 1 patients (receiving cholecalciferol) showed a 40.7% increase in serum 25(OH)D level, while group 2 patients (without cholecalciferol therapy) showed a negative trend (p<0.001). In addition, group 1 patients showed higher neutrophil and lymphocyte counts (p=0.047;p=0.025), and a lower level of C-reactive protein (p=0.028). A negative association was found between 25(OH)D levels and CRP values and between 25(OH)D levels and the length of hospital stay. Conclusion. Adding cholecalciferol as a bolus dose to standard COVID-19 therapy has a positive effect on the disease's clinical course and inflammatory markers' levels. Copyright © K.A. GOLOVATYUK, T.L. KARONOVA, A.A. MIKHAILOVA, D.I. LAGUTINA, A.T. CHERNIKOVA, E.YU. VASILIEVA, E.V. SHLYAKHTO.

Vitamin D status and COVID-19 prevention in a worker subgroup in Italy.

BACKGROUND: Low levels of vitamin D are widespread in the world's population and associated with sun exposure, genetics, and lifestyles. Office workers in different occupational sectors seem more vulnerable than others. Scientific evidence reports a contribution of vitamin D in resistance to infections, opening to supplementation as a preventive action against pathogens, including SARS-CoV-2. OBJECTIVE: A pilot campaign in the workplace during the coronavirus 2019 (COVID-19) pandemic was conducted based on the preliminary measurement of vitamin D amount and its integration. METHODS: A preventive action to contrast the deficiency of vitamin D was offered to a population of 700 bank employees. Vitamin D supplementation was performed between April and June 2021, on workers (n = 139) and showed 25(OH)D serum levels ≤ 30 ng/ml. Demographic, anthropometric and lifestyle information were collected by survey and changes in the serum 25(OH)D amounts were monitored. RESULTS: The adherence of the target population to the prevention campaign was 21%. 75% of the enrolled workers had low levels of vitamin D. After the intervention, serum vitamin D levels increased (1.28-fold;p = 0.0001) and 80% of the subjects reported optimal values > 30 ng/ml. Only 2.9% reported slight flu-like symptoms, but only 0.7% was confirmed as COVID-19, with respect to a ten-fold higher incidence in the general population. CONCLUSIONS: Vitamin D supplementation can be achieved by simple and noninvasive approaches and can bring along further insights into health literacy on diet and lifestyles, representing an opportunity to protect the population by the widespread state of vitamin deficiency.

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.

Correlation between 25-hydroxyvitamin D/D3 Deficiency and COVID-19 Disease Severity in Adults from Northern Colorado.

Vitamin D deficiency is common in the United States and leads to altered immune function, including T cell and macrophage activity that may impact responses to SARS-CoV-2 infection. This study investigated 131 adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR and 18 adults with no COVID-19 diagnosis that were recruited from the community or hospital into the Northern Colorado Coronavirus Biorepository (NoCo-COBIO). Participants consented to enrollment for a period of 6 months and provided biospecimens at multiple visits for longitudinal analysis. Plasma 25-hydroxyvitamin D levels were quantified by LC-MS/MS at the initial visit (n = 149) and after 4 months (n = 89). Adults were classified as deficient (<30 nM or <12 ng/mL), insufficient (<30−50 nM or 12−20 ng/mL), or optimal (50−75 nM or >20 ng/mL) for 25-hydroxyvitamin D status. Fisher's exact test demonstrated an association between disease severity, gender, and body mass index (BMI) at baseline. Mixed model analyses with Tukey-Kramer were used for longitudinal analysis according to BMI. Sixty-nine percent (n = 103) of the entire cohort had optimal levels of total 25(OH)D, 22% (n = 32) had insufficient levels, and 9% (n = 14) had deficent levels. Participants with severe disease (n = 37) had significantly lower 25-hydroxyvitamin D (total 25(OH)D) when compared to adults with mild disease (p = 0.006) or no COVID-19 diagnosis (p = 0.007). There was 44% of the cohort with post-acute sequalae of COVID-19 (PASC) as defined by experiencing at least one of the following symptoms after 60 days' post-infection: fatigue, dyspnea, joint pain, chest pain, forgetfulness or absent-mindedness, confusion, or difficulty breathing. While significant differences were detected in 25-hydroxyvitamin D status by sex and BMI, there were no correlations between 25-hydroxyvitamin D for those without and without PASC. This longitudinal study of COVID-19 survivors demonstrates an important association between sex, BMI, and disease severity for 25-hydroxyvitamin D deficiency during acute stages of infection, yet it is not clear whether supplementation efforts would influence long term outcomes such as developing PASC.

Vitamin D Supplementation and COVID-19 Outcomes: Mounting Evidence and Fewer Doubts.

The coronavirus disease 2019 (COVID-19) has already killed more than 6 million people around the world. A growing body of epidemiological evidence suggests that low 25-hydroxy vitamin D (25-OH-vitamin D) plasma levels are associated with an increased risk of developing COVID-19 and -most importantly-with a higher risk of developing more severe COVID-19 and dying. On the other hand, vitamin D supplementation during the early phases of COVID-19 has been related to a decreased length of hospital stay, less frequent need for oxygen, and a reduced mortality rate in inpatients. This seems to be particularly true when high dosages are used. In light of this evidence, further studies are needed to define the best timing for vitamin D supplementation and the most effective dosage schedule.

Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of 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.

Importance and role of vitamin D in pharmaceutical practise

The first scientific approach to vitamin D was made in the first half of the 20th century. The discovery had an important impact on the prevention and treatment of rickets, as well as enabling the knowledge and documentation of its role in regulating the balance of calcium-phosphate metabolism. Further reports have also suggested other health-relevant properties of vitamin D, including effects on: muscular, nervous, immune, cardiovascular, carbohydrate metabolism, obesity, cancer risk, and (relevant today) the issue of effects on the course and incidence of COVID-19. Six forms of vitamin D differing in the structure of the side chains was identified. The vitamin D group includes: cholecalciferol (vitamin D3) of animal origin or occurring in fungi ergocalciferol (vitamin D2). Vitamin D deficiency leads to rickets, osteomalacia and osteoporosis. Vitamin D supplementation allows, among other things, to reverse muscular atrophy, due to the fact that expression of the gene encoding VDR decreases with age. Insufficient synthesis of vitamin D or its low supply from diet can influence the development of cognitive disorders. A positive effect of the vitamin has been observed in the treatment of psoriasis and in obstructive diseases (asthma, chronic obstructive pulmonary disease). A special risk group for vitamin D deficiency are obese people who, according to recommendations, require an increased dose of vitamin D relative to the dose recommended for people with normal body weight. Supplementation should be conducted with simultaneous control of 25(OH)D3 metabolite concentration in blood. In supplementation and treatment of vitamin D deficiency in Poland and Europe mainly cholecalciferol (D3) is used, on American market also ergocalciferol (D2) is popular. The aim of this manuscript is to introduce the role and importance of vitamin D in pharmaceutical practice. High popularity of preparations containing vitamin D does not go hand in hand with the state of knowledge of patients and medical personnel, therefore, in addition to the role and function, the article also focuses on the problem of vitamin D deficiency (and its causes), recommendations of supplementation, and discusses toxicological issues. © Polskie Towarzystwo Farmaceutyczne.

Cholecalciferol level and its impact on COVID-19 patients.

BACKGROUND: Cholecalciferol is an important nutrient and essential to build body, maintain strong bones, and improves immunity.The main source for vitamin D is the body's skin which absorbs the sun's ultraviolet rays and convert them into vitamin D; at the same time, deficiency can occur or people may not get enough supplementation; this occurs mainly in old age, not taking healthy food, or have darker skin, and this deficient cases can raise the risk of severe COVID-19 if infected.Vitamin D boosts immunity and decreases inflammation. Poorer outcome of corona virus-disease (COVID-19) has been suggested to be due to vitamin D deficiency.We suggested to find the effect of cholecalciferol levels 25-hydroxy vitamin D (25 OHD) on the severity and mortality in patients suffering from COVID-19. METHODS: Our study is a prospective following of 414 patients admitted in Helwan University Hospitals in the period of June 2020 till October 2021 for severely symptomatic. COVID-19 patients with median of age 54.55 ± 14.27, with a definite range of APACHE II score ranging from 15 to 19 where we measured vitamin D3 level (cholecalciferol level), correlating the assay level to the inflammatory cytokine storm markers on admission, on the fifth day and after 10 days also the level of vitamin D3 was correlated to the length of stay mechanical ventilation days and mortality. RESULTS: Lower level of vitamin D3 on admission was strongly evident in patients with severely symptomatic and in mortality of COVID-19 patients 58.25 ± 24.59 nmol/L when compared with patients who survived 103.97 ± 36.14 nmol/L with P value < 0.001.Also, when correlating the initial level of vitamin D3 on admission with the level of the inflammatory cytokine storm markers on admission, on fifth day from admission and on the tenth day, it shows a strong inverse correlation between vitamin D3 level on admission and ferritin level on fifth day ρ-0.739 p value < 0.001 also on the tenth day ρ-0.885, P value < 0.001, in comparing also with D-dimer on fifth day ρ-0.858, p value < 0.001 also showing a strong inverse correlation with a highly significant p value this also evident on the D-dimer level on the tenth day ρ-0.889 with p value < 0.001, CRP at fifth and tenth day ρ-0.868, P value < 0.001, ρ-0.891, P value < 0.001 respectively also in correlating the LDH level on the fifth and tenth day with the initial level of vitamin D3 it shows a strong inverse correlation with a highly significant p value. ρ-0.887, P value < 0.001, ρ-0.878, p value < 0.001 respectively, in the fifth and tenth day. Neutrophil to lymphocyte ratio was strongly, inversely correlated to the vitamin D3 level (cholecalciferol) on admission with ρ-0.753, p < 0.001, ρ-0.882, P < 0.001 respectively. Also, chest computed tomography in the fifth and tenth day of admission showed a very strong inverse correlation with vitamin D level and a highly significant statistical difference ρ-0.655, p value < 0.001 respectively.Length of stay and mechanical ventilation days were also strongly inversely correlated to the cholecalciferol level ρ-0.795, p < 0.001, ρ- 0.879, P < 0.001 ROC curve of vitamin D3 to predict mortality (RR 0.865, 95% CI 0.828-0.896, P < 0.001, with cut off-value for vit. D3 < 60 nmol/L, regardless of other factors like age, gender, and presence of other co-morbidities. CONCLUSION: Low level of cholecalciferol was strongly inversely correlated with cytokine storm markers and independent predictor of severity and mortality in COVID-19 patients.

A case report on management of severe acute respiratory infection (Sari) with pericardial effusion in a case with hypothyroidism, hypertension and type-2 diabetes mellitus

Background: Severe Acute Respiratory Infections is acute respiratory infection with fever, cough, shortness of breath, or difficulty in breathing requiring admission to hospital. Hypothyroidism is a most common cause of pericardial effusion & it can also cause cardiac tamponade in severe cases. Patient Information: A 68 year old women registered to the EMD with history of chest pain and weakness for 3 days, she was known case of Hypertension and Hypothyroidism from last 3 years and Diabetes Mellitus (DM) Type 2 since 25 years, on medication. Diagnosis: After all general, physical examination and investigation done and she has diagnosed a Severe Acute Respiratory Infections With Pericardial Effusion. Therapeutic Management and Outcomes: Inj. Insulin R, inj. Levoflox 50 mg OD,inj. Meropenem 1gm TDS, Inj. Doxy 10 mg BD, Inj. Lasix 20 mg BD, tab. Thyrox 75 mg OD, tab. Ecosprin AV 75/20 HS, Tab. Thyrox 75 Mg Od, Tab. Telma H Od, Tab Dolo 650 Mg Stat, Syp. Kesol 2 tsp Tds, Tab. Metornol 25 Mg bd, Vitamin D3 60000 IU Once A Week, vitamin c & Zinc supplement was given. All the treatment was taken and she recovered slowly from symptoms.

Behaviours to strengthen immune system in the COVID-19 pandemic

Introduction and objective. Prevention of Sars-CoV-2 infection aims primarily on actions to limit the spread of the virus. However, many people have taken steps to improve the functioning of the immune system. The aim of the study was to assess individual behaviours strengthening immunity during the COVID-19 pandemic. Materials and method. The study was conducted in 2020, in a group of 245 adult Poles: 208 females (84.9%) and 37 males (15.1%). The respondents completed an author constructed questionnaire via the Internet concerning physical activity, the frequency of consumption of selected products and dietary supplements used, as well as preventive behaviours in connection with the COVID-19 pandemic. Statistical analysis was carried out using the Statistica 13.0. The chi-square test was used to evaluate the differences between groups;the level of statistical significance was set at p < 0.05. Results. A statistically significant increase was observed in the number of respondents (p < 0.001) who were vaccinated against influenza in the current season (6.0% in 2019/20 vs. 28.0% in 2020/21). Respondents associated with health care were most frequently vaccinated (48% vs. 36% of students and 14% of those not related to the health sector), and the differences between groups in both analyzed periods were statistically significant. Probiotics were taken by 9.0% of respondents, 56.7% supplemented vitamin D3, and 38.0% vitamin C. Conclusions. Prophylactic activities in the studied group focused on vaccinations and immediate supplementation of vitamins: D and C. The percentage of vaccinated persons was higher among those working in the health sector.

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial.

BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 ).