Vitamin D deficiency in critically ill COVID-19 ARDS patients

Abstract

Background & Aims Vitamin D’s pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10 to 15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D 3 via enteral feeding. Results A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96 % suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10 to 15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥ 30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048). Conclusion The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.

Vitamin D in infectious complications in critically ill patients with or without COVID-19

“…On the contrary, no difference was observed in the vitamin D levels of those hospitalized and those admitted to the ICU, and furthermore, among the ICU patients, there were no significant differences in ICU clinical outcomes between patients with low and normal vitamin D levels [ 103 ]. Similar results were observed in another study, in which 96% of critically ill COVID-19 ARDS patients exhibited vitamin D deficiency; however, the low levels of 25(OH)D were not related to changes in clinical course, whereas the low levels of 1,25(OH)D were associated with prolonged mechanical ventilation [ 104 ].…”

“… Cut-off for vitamin D Patient cohort Outcome/Findings Reference <30 ng/mL 154 patients: 91 asymptomatic COVID-19 patients and 63 severely ill patients requiring ICU admission Vitamin D level is markedly low in severe COVID-19 patients [ 94 ] <10 ng/mL 42 patients with acute respiratory failure due to COVID-19, treated in Respiratory Intermediate Care Unit (RICU) Patients with severe vitamin D deficiency had a 50% mortality probability [ 96 ] <15.2 ng/mL 30 critically ill COVID-19 patients The low vitamin D group had an increased risk of 28-day ICU mortality [ 97 ] <50 nmol/L 50 patients admitted to the ICU No significant differences in ICU clinical outcomes (invasive and non-invasive mechanical ventilation, acute kidney injury and mechanical ventilation and hospital days) between patients with low and normal vitamin D levels [ 103 ] <30 ng/mL 26 critically ill COVID-19 ARDS patients 96% of critically ill COVID-19 ARDS patients suffered from vitamin D deficiency. Low vitamin D levels were not related to changes in clinical course [ 104 ] …”

“…Group 3: None, comparator 77 patients; Group 1: N = 29; Group 2: N = 16; Group 3: N = 32 Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly [ 106 ] 40,000 IU one-off dose or up to 350,000 IU (booster therapy) 444 COVID-19 patients. Cholecalciferol booster therapy: N = 151 Cholecalciferol booster therapy was associated with a reduced risk of COVID-19 mortality [ 107 ] 400,000 IU bolus oral cholecalciferol (200,000 IU administered in two consecutive days) Bolus: N = 36; Best available treatment: N = 55 Beneficial effect of cholecalciferol on outcome (transfer to ICU or death) [ 108 ] 200,000 IU as a loading dose and 10,000 IU daily via enteral feeding N = 26 critically ill COVID-19 ARDS patients Supplementation did not impact the biologically active metabolite 1,25(OH)D [ 104 ] Randomization to either vitamin D3 (loading dose, then 3200 IU/day) or placebo in a 1:1 ratio 2700 Recruiting. VIVID trial [ 111 ] 10,000 IU for 14 days 42 outpatients; Vitamin D: N = 22; Control: N = 20 On the 14th day, the supplemented group presented fewer symptoms compared to the control group [ 109 ] …”

“…In outpatients, 10,000 IU of vitamin D3, for 14 days resulted in fewer symptoms compared to the control group [ 109 ]. On the other hand, administration of 200,000 IU vitamin D3 as a loading dose and 10,000 IU daily thereafter via enteral feeding did not impact the biologically active metabolite 1,25(OH)D, prompting the authors to suggest that both forms should be included in monitoring vitamin D status, and future interventional studies should target the usefulness of calcitriol administration in COVID-19 patients [ 104 ]. A systematic review and meta-analysis on vitamin D supplementation and clinical outcomes in COVID-19, including 10 observational studies and 3 RCTs, concluded that vitamin D supplementation might be associated with improved clinical outcomes, especially when administered after the diagnosis of COVID-19 [ 110 ].…”

Immunological Response to SARS-CoV-2 Is Sustained by Vitamin D: A Case Presentation of One-Year Follow-Up

“…Furthermore, recently, a systematic review and meta-analysis indicated that low vitamin D status might be associated with an increased risk of COVID-19 infection [23]. Low vitamin D was also reported in critically ill COVID-19 ARDS patients, in which even the active form 1,25-dihydroxyvitamin D was found to be low [24]. This biochemical form mediates most of the endocrine effects of vitamin D, including immune-modulatory functions [25,26].…”