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All Studies   Meta Analysis   Recent:  
0 0.5 1 1.5 2+ Mortality 27% Improvement Relative Risk Ventilation 7% ICU time -94% Hospitalization time -41% Vitamin D  COVID-VIT  ICU PATIENTS  DB RCT Is very late treatment with vitamin D beneficial for COVID-19? Double-blind RCT 106 patients in Russia (May 2020 - January 2022) Longer ICU admission (p=0.001) and hospitalization (p=0.007) Bychinin et al., Scientific Reports, Nov 2022 Favors vitamin D Favors control

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

Bychinin et al., Scientific Reports, doi:10.1038/s41598-022-22045-y, COVID-VIT, NCT05092698
Nov 2022  
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RCT ICU patients in Russia, showing significantly increased lymphocyte counts with treatment. Mortality was lower but without statistical significance. 40% of patients were on mechanical ventilation at baseline in the treatment group, compared to 30% in the placebo group.
Authors state that there has been 6 RCTs for COVID-19 and vitamin D, however there was at least 23 at the time of publication:
Although the 27% lower mortality is not statistically significant, it is consistent with the significant 36% lower mortality [27‑43%] from meta analysis of the 66 mortality results to date.
Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 65% [41‑79%] lower risk vs. 38% [25‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.
This is the 23rd of 28 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000081.
This is the 99th of 116 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 38 sextillion). This study is excluded in the after exclusion results of meta analysis: very late stage study using cholecalciferol instead of calcifediol or calcitriol.
risk of death, 26.9% lower, RR 0.73, p = 0.18, treatment 19 of 52 (36.5%), control 27 of 54 (50.0%), NNT 7.4.
risk of mechanical ventilation, 7.4% lower, RR 0.93, p = 0.68, treatment 33 of 52 (63.5%), control 37 of 54 (68.5%), NNT 20.
ICU time, 93.8% higher, relative time 1.94, p = 0.001, treatment 52, control 54.
hospitalization time, 41.4% higher, relative time 1.41, p = 0.007, treatment 52, control 54.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Bychinin et al., 3 Nov 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Russia, peer-reviewed, 7 authors, study period 1 May, 2020 - 31 January, 2022, average treatment delay 9.0 days, dosage 60,000IU day 1, 5,000IU days 2-7, 8, 5,000IU days 9-14, 15, 5,000IU days 16-21, 22, 5,000IU days 23-28, trial NCT05092698 (history) (COVID-VIT).
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This PaperVitamin DAll
Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU
Mikhail V Bychinin, Tatiana V Klypa, Irina A Mandel, Gaukhar M Yusubalieva, Vladimir P Baklaushev, Nadezhda A Kolyshkina, Aleksandr V Troitsky
Scientific Reports, doi:10.1038/s41598-022-22045-y
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, doubleblind, 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: Identifier: NCT05092698.
Author contributions M.V.B., T.V.K., V.P.B. and A.V.T. designed research; M.V.B. conducted research and wrote the main manuscript text; T.V.K. and I.A.M. edited the paper; N.A.K. and G.M.Y. performed laboratory analyses. I.A.M. analyzed data and prepared figures; M.V.B. had primary responsibility for final content. All authors reviewed the manuscript. Competing interests The authors declare no competing interests.
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Late treatment
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