Association between vitamin D hypovitaminosis and severe forms of COVID-19.

OBJECTIVE: Hypovitaminosis D may be associated with an increased susceptibility to infection, more severe COVID-19 forms, and a higher risk of death. The objective of this study was to investigate any possible connections between vitamin D status [as measured by serum 25-hydroxyvitamin D (25(OH)D) levels] and COVID-19 severity. PATIENTS AND METHODS: In 2021, a cross-sectional study of consecutive adult COVID-19 patients was conducted. Anthropometric data, comorbidities, hospital setting, length of stay, respiratory support, outcome data, and vitamin D status were all evaluated. RESULTS: The length of hospitalization among participants (n = 74; mean age 57.64 ± 17.83 years, 55.4% male) was 18.58 ± 10 days, the majority of the hospital setting was a medical ward (67.6%), and the respiratory support in the form of mechanical ventilation was represented by 12.2%. Hypertension (54.1%), obesity (64.9%), and overweight (64.9%) were the most common cardiometabolic risk factors. In the study group, 44.6% of participants had severe vitamin D deficiency (< 30 nmol/l), while 8.1% had vitamin D insufficiency (50 - 74.9 nmol/l). Furthermore, patients with severe COVID-19 (semi-intensive care unit, intensive care unit) had significantly lower serum 25(OH)D levels (32.9 vs. 20.5 nmol/l; p = 0.007). Participants with severe vitamin D deficiency were older and had more prevalent hypertension, requiring mechanical ventilation; 24.2% experienced a fatal outcome. CONCLUSIONS: Severe vitamin D deficiency may contribute significantly to the influence of other cardiometabolic risk factors in COVID-19.

Microparticles expressing myeloperoxidase as potential biomarkers in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV).

To investigate presence of circulating myeloperoxidase-positive microparticles (MPO+MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS ≥ 1). Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls (p < 0.001, p < 0.01, p < 0.001, respectively), while concentrations of PTX3+ and HMGB1+MPO+MPs were significantly higher in active AAV compared to patients in remission. MPO+MPs expressing either PTX3 or HMGB1 were associated with BVAS (r = 0.5, p < 0.001; r = 0.3, p = 0.04, respectively). Significantly higher serum PTX3 levels were found in active- than in inactive AAV (p < 0.001), correlating strongly with BVAS (r = 0.7, p < 0.001). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO+MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO+MPs were associated with disease activity in the investigated patients. KEY MESSAGES: Myeloperoxidase-positive microparticles (MPO+MPs) are increased in plasma from patients with ANCA-associated vasculitis. Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls. MPO+MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.

Treatment of pregnant females with dexamethasone influences postnatal development of the adrenal medulla.

In the light of the mutual dependence between the adrenal cortex and medulla, the aim of this work was to examine whether glucocorticoid treatment of pregnant rats affects the development of the adrenal medulla of their offspring in the postnatal period. Pregnant rats were treated with dexamethasone (Dx) in a daily dose of 0.3 mg Dx/kg b.w. during days 16-20 of gestation. The structure and function of the adrenal medulla of their 14-day-old offspring were estimated on the basis of the morphometric parameters of the gland, chromaffin cell mitotic index and adrenal gland adrenaline content. Stereological analysis was carried out at the light microscopic level, the mitotic index was determined by counting the number of metaphase arrested chromaffin cells following the administration of vincristine-sulphate, whereas adrenaline content in the adrenal gland was measured fluorimetrically. Plasma ACTH concentrations of the offspring were also determined by RIA. Long term Dx treatment of pregnant rats caused a significant decrease of the total volume of adrenal chromaffin tissue in the 14-day-old offspring as well as a reduction in the number of chromaffin cells and the average cell and nuclear volumes. The proliferative activity of the chromaffin cells was also lower than in the control offspring. These changes were accompanied by a significantly reduced adrenaline content in the adrenals. The results of this work show that glucocorticoid excess during the period of pregnancy when the fetal adrenal medulla is formed has a strong inhibitory effect on the adrenal medulla of the offspring at the age of 14 days.

The influence of prolonged dexamethasone treatment of pregnant rats on the perinatal development of the adrenal gland of their offspring.

The effects of prolonged dexamethasone (Dx) administration to pregnant rats on the structure and function of the adrenal glands of fetal and neonatal offspring have been investigated by combined stereological and ultrastructural methods, as well as by metaphase index determination. Pregnant rats were injected subcutaneously with Dx (0.3 mg/kg body weight/day) during 5 days, starting from day 16 of gestation. The dams and their fetuses were killed 24 hr after the last injection. The neonatal offspring were killed in the same way on the 3rd and 14th day of life. Because in fetal and 3-day-old neonatal rats zona reticularis (ZR) was poorly defined and could not be clearly seen as a separate zone, zona fasciculata (ZF) and ZR were analyzed as one, inner zone (IZ). In 14-day-old rats ZF and ZR were analyzed separately. Proliferative activity of adrenocortical cells was estimated following the application of Vincristine sulphate. Dx treatment of pregnant rats induced a marked decrease of fetal adrenal gland volume and the volumes of zona glomerulosa + capsula (ZG + C) and IZ as the consequence of atrophic changes in the gland and reduction of the average volume and total number of adrenocortical cells. Similar morphometric changes were found in 3- and 14-day-old pups. However, in 3-day-old animals the number of cortical cells in the ZG was increased, whereas on the 14th postnatal day cortical cell number remained decreased only in the ZF. The multinuclear giant cells, numerous lymphocytes, and the resorption zones, present in the adrenal cortex of fetuses and 3-day-old pups of both experimental and control dams, were not seen in 14-day-old offspring. These results demonstrate that prolonged treatment of pregnant rats with Dx in the period when intensive differentiation of the fetal hypothalamo-hypophyseal system takes place inhibits proliferative activity of adrenocortical cells and evokes considerable atrophic changes in the adrenal glands of offspring from 20 days gestation to 14 days after birth. The histological appearance of the adrenal cortex and the ultrastructure of adrenocortical cells suggest that cortical cell function was inhibited.