Impaired Vitamin D Metabolism in Hospitalized COVID-19 Patients.

There is increasing data regarding the association between vitamin D and COVID-19. This study aimed to reveal the alterations of vitamin D metabolism in the setting of COVID-19. We examined 119 adult COVID-19 inpatients and 44 apparently healthy adult individuals with similar serum 25OH-D3 levels as a reference group. The assessment included serum biochemical parameters (total calcium, albumin, phosphorus, creatinine), parathyroid hormone (PTH), vitamin D-binding protein (DBP), vitamin D metabolites (25OH-D3, 25OH-D2, 1,25(OH)2D3, 3-epi-25OH-D3, 24,25(OH)2D3 and D3) and free 25OH-D. COVID-19 patients had in general very low vitamin D levels (median 25OH-D3 equals 10.8 ng/mL), accompanied by an increased production of the active vitamin D metabolite (1,25(OH)2D3), estimated as higher 1,25(OH)2D3 serum levels (61 [44; 81] vs. 40 [35; 50] pg/mL, p < 0.001) and lower 25OH-D3/1,25(OH)2D3 ratio (175 [112; 260] vs. 272 [200; 433], p < 0.001) which is presumably aimed at preventing hypocalcemia. Patients with COVID-19 also had elevated DBP (450 [386; 515] vs. 392 [311; 433] mg/L, p < 0.001) and low free 25OH-D levels (<LoB vs. 3.9 [3.2; 4.4] pg/mL, p < 0.001). Follow-up assessment of the COVID-19 inpatients showed recovery of the observed changes. Overall, hospitalized patients with an acute course of COVID-19 have not only very low levels of 25OH-D but also profound abnormalities in the metabolism of vitamin D regardless of the clinical course of the disease. These alterations might exacerbate existing vitamin D deficiency and its negative impact.

Vitamin D Metabolism Is Significantly Impaired in COVID-19 Inpatients

Objective: to assess the state of vitamin D metabolism in patients hospitalized with COVID-19 infection. Materials and methods: We examined 49 patients, which were hospitalized for inpatient treatment of COVID-19 infection from May to June 2020. Study group included 24 men (49%) and 25 women (51%), median age 58 years [48;70], BMI 26.4 kg/m2 [24.3;30.5]. All patients were diagnosed with pneumonia due to SARS-CoV-2 with median percent of lung involvement equal to 29% [14;37], 22 patients (45%) required oxygen support upon admission. Median SpO2 was equal to 95% (92;97), median NEWS score was equal to 3 [2;6]. Participants were tested for vitamin D metabolites (25(OH)D3, 1,25(OH)2D3, 3-epi-25(OH)D3, 24,25(OH)2D3 and D3) by UPLC-MS/MS, free 25(OH)D and vitamin D-binding protein by ELISA, as well as PTH by electrochemiluminescence immunoassay and routine biochemical parameters of blood serum (calcium, phosphorus, albumin) at the time of admission. Results: patients had in general very low 25()D3 levels - median 10.9 ng/mL [6.9;15.6], corresponding to a pronounced vitamin D deficiency in half of the patients. Levels of 24,25(OH)2D3 were also low – 0.5 ng/mL [0.2;0.9], and resulting vitamin D metabolite ratios (25(OH)D3/24,25(OH)2D3) were high-normal or elevated in most patients – 24.1 [19.0;39.2], indicating decreased activity of 24-hydroxylase. Levels of 1,25(OH)2D3, on the contrary, were high-normal or elevated - 57 pg/mL [46;79], which, in accordance with 25(OH)D3/1,25(OH)2D3 ratio (219 [134;266]) suggests an increase in 1α-hydroxylase activity. Median level of 3-epi-25(OH)D3 was 0.7 ng/mL [0.4;1.0] and D3 metabolite was detectable only in 6 patients. Median DBP level was 432 mg/L [382;498], median free 25(OH)D was 5.6 pg/mL [3.3;6.7], median calculated free 25(OH)D was 2.0 pg/mL [1.4;3.3]. Most patients had albumin-adjusted serum calcium level in the lower half of reference range (median 2.24 mmol/L [2.14;2.34]). Seven patients had secondary hyperparathyroidism and one patient had primary hyperparathyroidism, the rest of the patients had PTH levels within the normal range.25(OH)D3 levels showed significant negative correlation with percent of lung involvement (r = -0.36, p&lt;0.05) and positive correlation with SpO2 (r = 0.4, p&lt;0.05). 1,25(OH)2D3 levels correlated positively with 25(OH)D3 levels (r = 0.38, p&lt;0.05) and did not correlate significantly with PTH levels (p&gt;0.05). Conclusion: Our data suggests that hospitalized patients with COVID-19 infection have significant impairment of vitamin D metabolism, in particular, an increase in 1α-hydroxylase activity, which cannot be fully explained by pre-existing conditions such as vitamin D deficiency and secondary hyperparathyroidism. The observed profound vitamin D deficiency and association of vitamin D levels with markers of disease severity indicate the importance of vitamin D supplementation in these patients.