Dexamethasone treatment may mitigate adverse effects of vitamin D deficiency in hospitalized Covid‐19 patients

Abstract

Aims We have previously demonstrated that vitamin D deficiency might be associated with worse outcomes in hospitalized Covid‐19 patients. The aim of our study was to explore this relationship with dexamethasone therapy. Methods We prospectively studied two cohorts of hospitalized Covid‐19 patients between March and April and between September and December 2020 ( n = 192). Patients were tested for serum 25‐hydroxyvitamin D (25‐OH‐D) levels during admission. The first cohort not treated with dexamethasone ( n = 107) was divided into vitamin D deficient (25‐OH‐D ≤ 30 nmol/L) ( n = 47) and replete subgroups (25‐OH‐D > 30 nmol/L) ( n = 60). The second cohort treated with dexamethasone ( n = 85) was similarly divided into deficient (25‐OH‐D ≤ 30 nmol/L) ( n = 27) and replete subgroups (25‐OH‐D > 30 nmol/L) ( n = 58). Primary outcome was in‐hospital mortality and secondary outcomes were elevation in markers of cytokine storm and ventilatory requirement. Results No mortality difference was identified between cohorts and subgroups. The “no dexamethasone” cohort 25‐OH‐D deplete subgroup recorded significantly higher peak d ‐Dimer levels (1874 vs. 1233 µgFEU/L) ( p = 0.0309), CRP (177 vs. 107.5) ( p = 0.0055), and ventilatory support requirement (25.5% vs. 6.67%) ( p = 0.007) compared to the replete subgroup. Among the 25‐OH‐D deplete subgroup higher peak neutrophil counts, peak CRP, peak LDH, peak ferritin, and lower trough lymphocyte counts were observed, without statistical significance. In the “dexamethasone” cohort, there was no apparent association between 25‐OH‐D deficiency and markers of cytokine storm or ventilatory requirement. Conclusion: Vitamin D deficiency is associated with elevated markers of cytokine storm and higher ventilatory requirements in hospitalized Covid‐19 patients. Dexamethasone treatment appears to mitigate adverse effects of vitamin D deficiency.

The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2

“…The complex interaction of Vit D and corticosteroids (CRTs) in vivo may partially explain the conflicting outcomes observed in the COVID-19 literature, and previous studies on Vit D have been insufficiently powered to detect this interaction [ 55 , 56 , 57 , 58 , 59 ]. Glucocorticoids can inactivate Vit D by upregulating Vit D receptor (VDR)-mediated 24-hydroxylase transcription through the cooperative relationship of CCAAT-enhancer-binding proteins (C/EBPβ) and glucocorticoid receptors (GRs) [ 60 ].…”

A Prospective Cohort Study of COVID-19: Evaluation of the Early Role of IL-1 and IL-6 Antagonists in Improving the Outcome of the Illness and Reduction in the Risk of Death

“…Studies have shown that the use of dexamethasone in COVID-19 patients can lead to a reduction in D-dimer levels [ 76 , 77 ]. While some studies have suggested that dexamethasone can reduce D-dimer levels in COVID-19 patients [ 78 , 79 ], other studies have found no significant effect [ 80 , 81 , 82 ]. While there have been some studies that have shown a reduction in D-dimer levels with the use of IL-6 antagonists in COVID-19 patients, other studies have found no significant effect on D-dimer levels.…”

Evaluating the Evidence in Clinical Studies of Vitamin D in COVID-19

“…Vitamin D status may interact with other treatments for COVID-19. Investigators in the UK compared outcomes associated with vitamin D status before (March–April 2020) and after (September–December 2020) the use of dexamethasone in hospitalized patients [ 30 ]. Vitamin D deficiency was associated with elevated CRP and need for ventilation in hospitalized COVID-19 patients prior to use of dexamethasone but not during the interval of dexamethasone use.…”