Serum vitamin D levels and inflammatory status in COVID-19 patients.

OBJECTIVES: The coronavirus 2019 disease (COVID-19) is characterized by a heterogeneous clinical presentation, a complex pathophysiology and a wide range of laboratory findings, depending on disease severity. BACKGROUND: We studied some laboratory parameters in correlation with vitamin D status representing the inflammatory state in hospitalized COVID-19 patients on admission. METHODS: The study included 100 COVID-19 patients with moderate (n=55) and severe (n=45) form of the disease. Complete blood count and differential blood count, routine biochemical parameters, C-reactive protein and serum procalcitonin, ferritin, human IL-6 and serum vitamin D (measured as 25-OH vitamin D) concentrations, were performed. RESULTS: According to the severity of the disease, patients with severe form had significantly lower serum vitamin D (16.54±6.51 ng/ml vs 20.37±5.63 ng/ml, p=0.0012), higher serum interleukin-6 (41.24±28.46 pg/ml vs. 24.75±16.28 pg/ml, p=0.0003), C-reactive protein (101.49± 57.15 mg/l vs 74.43±42.99 mg/l, p=0.0044), ferritin (969.89±338.37 ng/ml vs 845.96±359.91 ng/ml, p=0.0423) and LDH (1050.53±369.11 U/l vs 905.31±335.57 U/l, p=0.0222) compared to those with moderate form of the disease. CONCLUSION: The presented data provide a relationship between increased inflammatory laboratory markers, low vitamin D levels and disease severity in COVID-19 patients (Tab. 2, Fig. 3, Ref. 32).

The relationship between vitamin D deficiency and mortality in older adults before and during COVID-19 pandemic.

BACKGROUND: Vitamin D is an essential fat-soluble vitamin thought to be associated with chronic diseases, mortality and COVID-19. OBJECTIVE: To investigate the association between 25(OH) vitamin D levels and mortality of chronic diseases in subjects aged ≥65 years before and during COVID-19 pandemic. METHODS: A single-center, retrospective study was performed using the hospital database of subjects aged 65 years and older who had undergone vitamin D measurement between 01.01.2019 and 31.12.2021. All patients with vitamin D measurement (N = 2155) were followed as a cohort from the date of serum vitamin D analysis through death date or 01.01.2022. Age, gender, chronic diseases, survival status, date of death of the deceased, laboratory values including complete blood count, liver/renal functions and 25(OH) vitamin D levels were all noted. Subjects were classified into three groups according to their 25(OH) vitamin D levels; severe deficient group (<10 ng/ml), moderate deficient group (10-19.9 ng/ml), and control group (≥20 ng/ml). RESULTS: Data of 1949 subjects were included in this retrospective analysis and 206 of them (10.6%) had at least two vitamin D measurements. Until the time of data collection (01.01.2022), 94 of the cases had died within the last three years, and only five of them had repeated measurements. While the mean vitamin D level was lower, age and frequency of dyslipidemia, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), arrhythmia, dementia and severe vitamin D deficiency (<10 ng/ml) were higher in subjectswho died (all p<0.05). According to the Cox proportional hazards model; age, presence of CAD, COPD, arrhythmia, dementia, anemia and severe vitamin D deficiency were independently related with mortality (all p<0.05). After adjusted by age, gender, and comorbidities, the probability of death was found to be 1.91 (95% CI=1.12-3.24) times higher in the severe vitamin D deficient group. CONCLUSIONS: The results of this study have shown that - after having adjusted for potential factors - severe vitamin D deficiency (<10 ng/ml) seems to be an independent predictor for non-cancer mortality. Although vitamin D measurement/treatment is very easy and cheap where, on the contrary, severe vitamin D deficiency can be quite mortal.

The Impact of Vitamin D Deficiency on the Severity of Symptoms and Mortality Rate among Adult Patients with Covid-19: A Systematic Review and Meta-Analysis.

INTRODUCTION: We aimed to study the prevalence of vitamin D deficiency (VDD) in patients with COVID-19 infection and evaluate the impact of vitamin D levels on the severity of symptoms and the case fatality rate. EVIDENCE ACQUISITION: A comprehensive literature search was performed up to December 20, 2020, using the following databases: MEDLINE, PubMed, EMBASE, SCOPUS, Web of Science, and preprint databases (BioRxiv and MedRxiv). Any individual observational study related to the prevalence and impact of vitamin D deficiency/insufficiency (VDD/VDI) on the severity of COVID-19 symptoms and mortality rates was included. No language restrictions were applied, and both published and non-published studies were included. EVIDENCE SYNTHESIS: Two of the authors independently performed the literature search and assessed the eligibility of studies. The quality of studies included was assessed using the Newcastle-Ottawa Scale. Data were analyzed using the Review Manager Software (version 5) and Comprehensive Meta-analysis Software (version 3). A total of 43 studies were included with a sample size of 254,963 patients with COVID-19. Pooled analysis showed a higher prevalence of VDD and VDI in patients with COVID-19 (59.0% and 40.1%, respectively). Moreover, a significant association was noticed between vitamin D levels and severity of symptoms (odds ratio [OR] = 3.38, 95% confidence interval [CI]: 1.94-5.87, P < 0.0001), as well as the case fatality rate (OR = 2.30, 95% CI: 1.47-3.59, P < 0.00001). CONCLUSIONS: VDD is highly prevalent in patients with COVID-19 infection. Lower vitamin D levels correlate with disease severity and poor prognosis although most of the data have been derived from moderate-quality observational studies.

Correlation between 25-hydroxy vitamin D levels and COVID-19 severity in pregnant women: a cross-sectional study.

OBJECTIVE: To evaluate the relationship between 25-hydroxy vitamin D (25(OH)D) levels and disease severity in hospitalized COVID-19 positive pregnant women. METHODS: The COVID-19 (+) pregnant women (confirmed by PCR test) were classified as asymptomatic, mild symptomatic, and severe disease according to their symptoms and laboratory results. Severe COVID-19 criteria were respiratory symptoms and/or findings. The following laboratory results were considered as poor prognostic factors: the number of lymphocytes <800/µl and/or CRP value >10 times the upper limit of the normal range and/or ferritin value >500 ng/ml and/or D-Dimer value >1000 µg/l. The patients were divided into two groups; asymptomatic or mild symptomatic group (Group 1), and severe disease and/or poor prognostic factor group (Group 2). The 25(OH)D levels were compared between groups. ROC curve analysis was used to analyze the cutoff value for vitamin D to predict the severity of COVID-19. RESULTS: 25(OH)D levels were found to be statistically significantly lower in group 2 (15.5 (10.25) ng/ml in Group 1, 13 (12) ng/ml in Group 2, p = .010). The 25(OH)D level under 14.5 ng/ml was associated with severe COVID-19 and/or poor prognostic factors (p = .010). The risk of severe COVID-19 and/or having poor prognostic factors was 1.87 times higher among pregnant women who had 25(OH)D levels below 14.5 ng/ml. This value was found to have 54.1% sensitivity and 61.3% specificity in predicting severe COVID-19 and/or poor prognostic laboratory findings in pregnant women. CONCLUSION: There is a relationship between vitamin D status and the severity of COVID-19 in pregnant women. During the pandemic period, vitamin D supplementation for pregnant women should gain more importance.

Seasonal UV exposure and vitamin D: association with the dynamics of COVID-19 transmission in Europe.

Several recent studies have demonstrated that low plasma 25(OH) vitamin D levels are associated with the risk of COVID-19 infection. The primary source of vitamin D production in humans is environmental UV radiation. In many viral respiratory diseases, peak infection rates are observed during winter due to reduced UV exposure and low temperatures. In Europe, the second wave of COVID-19 began early in the winter of 2020. Investigating the impact of seasonal temperature and UV exposure on COVID-19 transmission could thus aid in prevention and intervention. As such, we first performed a comprehensive meta-analysis of all related published literature based on the association between vitamin D and COVID-19, which supported the hypothesis that the low vitamin D level is a critical risk factor for COVID-19 infection. Next, to understand the potential impact of seasonal UV and temperature levels on COVID-19 cases, we analyzed meteorological data and daily COVID-19 cases per million in the populations of 26 European countries. We observed that low temperature, UV index, and cloud-free vitamin D UV dose (UVDVF) levels are negatively correlated with COVID-19 prevalence in Europe. Furthermore, a distributed lag nonlinear model was used to assess the nonlinear delayed effects of individual seasonal factors on COVID-19 cases. Such analysis highlighted the significantly delayed impact of UVDVF on the cumulative relative risk of COVID-19 infection. The findings of this study suggest that low UV exposure can affect the required production of vitamin D in the body, which substantially influences the dynamics of COVID-19 transmission and severity.

Serum 25-hydroxyvitamin D measurement: Comparative evaluation of three automated immunoassays.

OBJECTIVES: the different analytical methods for measurement of serum 25-hydroxyvitamin D (25(OH)D) are not yet fully harmonized and no consensus exists on a threshold of 25(OH)D defining a deficiency status. In this study, we compared the results from the assays of serum 25(OH)D performed with three different methods to evaluate the presence of potential biases and how much these biases can influence the assignment of patients to specific 25(OH)D deficiency/sufficiency categories. DESIGN AND METHODS: Liaison 25(OH) Vitamin D Total (DiaSorin Liaison XL), Elecsys Vitamin D Total II (Roche Elecsys) and Lumipulse G25(OH) Vitamin D (Fujirebio Lumipulse G1200) were used. Methods comparability was established performing Passing-Bablok regression and Bland-Altman analysis to prove whether the differences found were lower than the preliminarily pre-established maximum acceptable bias. RESULTS: all Passing-Bablok regressions exhibited the presence of a proportional and constant systematic error. Bland-Altman analysis revealed biases well above the maximum acceptable bias, so the 25(OH)D concentrations measured were not comparable. To evaluate whether the three methods had the same ability to classify patients into different categories of vitamin D levels, we categorized results obtained by each method in reference classes. Lumipulse categorized most patients into the class with the lowest 25(OH)D concentrations (<20 ng/mL) whereas Elecsys ranked the lowest number. CONCLUSIONS: Liaison XL and Elecsys have shown good accuracy compared to Lumipulse in measuring 25(OH)D levels. Nevertheless, the assays were not interchangeable due to the lack of comparability of results as well as to the disagreement in classification of hormone deficiency or sufficiency.

Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study.

Vitamin D deficiency is a worldwide pandemic. The aim of this study was to evaluate associations of plasma 25(OH)D levels with the likelihood of coronavirus disease 2019 (COVID-19) infection and hospitalization. The study population included the 14 000 members of Leumit Health Services, who were tested for COVID-19 infection from February 1st to April 30th , 2020, and who had at least one previous blood test for the plasma 25(OH)D level. 'Suboptimal' or 'low' plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below the level of 30 ng/mL. Of 7807 individuals, 782 (10.02%) were COVID-19-positive, and 7025 (89.98%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval (CI) 18.41-19.59) vs. 20.55 (95% CI: 20.32-20.78)]. Univariate analysis demonstrated an association between the low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI: 1.24-2.01, P < 0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI: 1.01-4.30, P < 0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI: 1.08-1.95, P < 0.001)] and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI: 0.98-4.845, P = 0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19. We concluded that low plasma 25(OH)D levels appear to be an independent risk factor for COVID-19 infection and hospitalization.

An Update on Vitamin D Metabolism.

Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver hydroxylase CYP2R1, the specificity of 1α-hydroxylase in different tissues and cell types and the genomic, non-genomic and epigenomic effects of vitamin D receptor, which will be addressed in the present review. Moreover, in the last decades, several extraskeletal effects which can be attributed to vitamin D have been shown. These beneficial effects will be here summarized, focusing on the immune system and cardiovascular system.

Micronutrients in COVID-19 Positive Pregnancies.

Pregnant women are considered among the high-risk population for COVID-19. Therefore, research for methods of treatment and prevention of COVID-19 positive pregnancies carries an importance. The aim of this study was to measure serum 25(OH)D, vitamin B12, and zinc levels in COVID-19 positive pregnant women to evaluate the role of these micronutrients in treatment and prevention. A total of 44 COVID-19 positive pregnant women who were hospitalized and treated at a tertiary clinic were included in this study. The mean serum 25(OH)D level was measured to be 9.70 ± 59.14. The mean serum zinc level was 62.58 ± 2.63, and the mean serum vitamin B12 level was 295.55 ± 302.48. All these variables were significantly lower than the accepted cut-off values (p < 0.001). These low values might have contributed to a deficiency in their immune response and thus made these patients susceptible to COVID-19 infection. Supplementation of micronutrients during the pandemic could be beneficial during pregnancy for prevention.