Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU

Abstract

Vitamin D as an immunomodulator has not been studied in patients with severe COVID-19. This study aimed to estimate the efficacy of vitamin D3 supplementation on cellular immunity and inflammatory markers in patients with COVID-19 admitted to the intensive care unit (ICU). A single-center, double-blind, randomized, placebo-controlled pilot trial was conducted (N = 110). Patients were randomly assigned to receive a weekly oral dose of 60,000 IU of vitamin D3 followed by daily maintenance doses of 5000 IU (n = 55) or placebo (n = 55). Primary outcomes were lymphocyte counts, natural killer (NK) and natural killer T (NKT) cell counts, neutrophil-to-lymphocyte ratio (NLR), and serum levels of inflammatory markers on 7th day of treatment. On day 7, patients in the vitamin D3 group displayed significantly higher NK and NKT cell counts and NLR than those in the placebo group did. The mortality rate (37% vs 50%, P = 0.16), need for mechanical ventilation (63% vs 69%, P = 0.58), incidence of nosocomial infection (60% vs 41%, P = 0.05) did not significantly differ between groups. Vitamin D3 supplementation, compared with placebo, significantly increased lymphocyte counts, but did not translate into reduced mortality in ICU.Trial Registration: ClinicalTrials.gov Identifier: NCT05092698.

Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials

“…All included studies are randomized controlled trials with a control group containing vitamin D3 supplementation. Among these studies, five studies had a placebo in the control group [20][21][22][23][24], four studies had no supplementation in the control group [25][26][27][28] and four studies had a standard dose of vitamin D3 [29][30][31][32]. Two studies included patients admitted to the intensive care unit [21,32].…”

Effect of vitamin D supplementation on COVID-19 patients: A systematic review and meta-analysis

“…The sample sizes of RCTs ranged from 43 to 543, with mean or median ages ranging from 10.7 to 69 years and follow-up from 7 days to 4 months ( 8 – 10 , 20 – 24 ). Cholecalciferol was administered in the intervention arm of six RCTs ( 9 , 10 , 20 – 22 , 24 ), while calcifediol ( 23 ) and calcitriol ( 8 ) were used in the remaining two RCTs. The sample sizes of the eight cohort studies ranged from 48 to 785, with mean ages ranging from 45.5 to 87.7 years, and follow-up from 5 days to 3 months.…”

“…Four RCTs had a low risk of bias ( 10 , 20 , 22 , 24 ), one was at a high risk of bias ( 21 ) and the rest three studies had an uncertain risk of bias ( 8 , 9 , 23 ) ( Supplementary Figures 1 , 2 ). Six cohort studies had a moderate risk of bias ( 5 , 12 , 13 , 25 – 27 ), and the other two had a serious risk of bias ( 6 , 11 ) ( Supplementary Figure 3 ).…”

“…The results revealed no significant differences in mortality between individuals with baseline 25OHD levels below 20 ng/ml (RR = 0.93, 95% CI 0.66-1.32, P = 0.68) (9, Forest plot of cohort studies for vitamin D supplementation on mechanical ventilation or intubation. 21, 22,24) and those with levels above 20 ng/ml (RR = 1.68, 95% CI 0.72-3.93, P = 0.23) (10,20), or between individuals receiving average daily vitamin D supplementation doses less than 4,000 IU (21, 24) (RR = 0.62, 95% CI 0.09-4.13, P = 0.63) and those receiving doses greater than 4,000 IU (9,10,20,22) (RR = 1.10, 95% CI 0.78-1.55, P = 0.58). However, the results from cohort studies indicated that there was a significant reduction in mortality among individuals receiving average daily vitamin D supplementation doses less than 4,000 IU (5, 6) (RR = 0.18, 95% CI 0.08-0.40, P < 0.001) and those receiving doses greater than 4,000 IU (11,12,25,27) (RR = 0.51, 95% CI 0.27-0.96, P = 0.037) (Figure 5).…”

Vitamin D Influences the Activity of Mast Cells in Allergic Manifestations and Potentiates Their Effector Functions against Pathogens

“…Patients with disorders impacting vitamin D’s metabolism, such as chronic renal failure and vitamin D-resistant rickets, have been found to have decreased NK cell activity. In these instances, NK cell activity improved and even returned to normal as a result of the vitamin D supplementation [ 20 ]. Studies have identified novel MC-derived molecules, in either a secreted or membrane-bound form, facilitate communication between various immune cells [ 21 ], such as T cells [ 22 ], B cells [ 23 ], NK cells [ 24 ], innate lymphoid cells [ 25 ], eosinophils [ 26 ], MQs [ 27 ], and DCs [ 28 ].…”