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All Studies   Meta Analysis       

The prognostic significance of vitamin D deficiency in patients with COVID-19 pneumonia

Yildiz et al., Bratislava Medical Journal, doi:10.4149/BLL_2021_119
Sep 2021  
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Mortality 81% Improvement Relative Risk ICU admission 94% Hospitalization time 10% Vitamin D for COVID-19  Yildiz et al.  LATE TREATMENT Is late treatment with vitamin D beneficial for COVID-19? Retrospective 207 patients in Turkey Lower mortality with vitamin D (p=0.038) c19early.org Yildiz et al., Bratislava Medical J., Sep 2021 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
Retrospective 207 hospitalized patients in Turkey, 37 with vitamin D levels <30ng/ml treated with a single dose of 300,000IU vitamin D, showing lower mortality with treatment.
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: 69% [47‑82%] lower risk vs. 39% [27‑49%] 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.
Bolus treatment is less effective. Pharmacokinetics and the potential side effects of high bolus doses suggest that ongoing treatment spread over time is more appropriate. Research has confirmed that lower dose regular treatment with vitamin D is more effective than intermittent high-dose bolus treatment for various conditions, including rickets and acute respiratory infections1,2. The biological mechanisms supporting these findings involve the induction of enzymes such as 24-hydroxylase and fibroblast growth factor 23 (FGF23) by high-dose bolus treatments. These enzymes play roles in inactivating vitamin D, which can paradoxically reduce levels of activated vitamin D and suppress its activation for extended periods post-dosage. Evidence indicates that 24-hydroxylase activity may remain elevated for several weeks following a bolus dose, leading to reduced levels of the activated form of vitamin D. Additionally, FGF23 levels can increase for at least three months after a large bolus dose, which also contributes to the suppression of vitamin D activation1.
This is the 55th of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
30 studies are RCTs, which show efficacy with p=0.0000032.
risk of death, 80.9% lower, RR 0.19, p = 0.04, treatment 1 of 37 (2.7%), control 24 of 170 (14.1%), NNT 8.8.
risk of ICU admission, 94.5% lower, RR 0.06, p = 0.13, treatment 0 of 37 (0.0%), control 14 of 170 (8.2%), NNT 12, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
hospitalization time, 9.6% lower, relative time 0.90, p = 0.32, treatment 37, control 170.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Yildiz et al., 27 Sep 2021, retrospective, Turkey, peer-reviewed, 5 authors, dosage 300,000IU single dose.
This PaperVitamin DAll
The prognostic significance of vitamin D deficiency in patients with COVID-19 pneumonia
M Yildiz, M U Senel, S Kavurgaci, F E Ozturk, A Ozturk
Bratislava Medical Journal, doi:10.4149/bll_2021_119
BACKGROUND: Vitamin D has anti-infl ammatory and immunomodulatory effects via the downregulation of pro-infl ammatory cytokines. We aimed to demonstrate the effect of vitamin D levels on survival in COVID-19 patients. MATERIALS AND METHODS: 207 COVID-19 patients were included in the study. Serum vitamin D levels were measured, and patients with levels < 20 ng/ml or 21 to 30 ng received a single 300.000 IU dose of vitamin D. RESULTS: Of 207 patients, 37 received vitamin D, while 170 did not. Demographic, radiologic and mean laboratory values were similar between the groups. The mean plasma vitamin D level without vitamin D support (n=170) was 50.82 ± 16.12 ng/ml (30.28 -81.35) vs. 16.98 ± 6.2 ng/ml (4.20 -28.30) in vitamin D group. The most remarkable fi nding were the mortality rates; while only 1 patient (2.7 %) died in the vitamin D group, 24 patients (14.1 %) died in no vitamin D supplementation group (p = 0.038). CONCLUSION: Although a few retrospective studies put forth a relation between vitamin D defi ciency and COVID-19 course severity there is still paucity of data about the effi cacy of vitamin supplementations in COVID-19 patients. A single 300.000 IU dose of vitamin D seems to represent a useful, practical, and safe adjunctive approach for the treatment or prevention of Fig. 1, Ref. 30).
References
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Hoffmann, Kleine-Weber, Schroeder, Kruger, Herrler et al., SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, doi:10.1016/j.cell.2020.02.052
Hunter, Jones, IL-6 as a keystone cytokine in health and disease, Nat Immunol
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Kong, Li, Effect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null mice, Am J Physiol Regul Integr Comp Physiol
Kong, Zhu, Shi, VDR attenuates acute lung injury by blocking 9Ang-2-Tie-2 pathway and renin-angiotensin system, Mol Endocrinol
Konya, Czarnewski, Forkel, Rao, Kokkinou et al., Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells, J Allergy Clin Immunol
Majumder, Torabi, Saeg, Hoffman, Cirillo et al., Vitamin D Insuffi ciency is Prevalent in Severe COVID-19, doi:10.1101/2020.04.24.20075838
Mar, Gülgün, Sule, Sargin, Comparison of Different Vitamin D Replacement Modalities in Vitamin D-Defi cient Patients, Turk J Endocrinol Metab
Martineau, Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ
Mcmurray, Bartow, Mintzer, Hernandez-Frontera, 1990Micronutrient statusandimmunefunction in tuberculosis, Ann NY Acad Sci
Michael, Neil, Heike, Endocrine Society. Evaluation, treatment, and prevention of vitamin D defi ciency: an Endocrine Society clinical practice guideline, J Clin Endocrinol Metab
Miroliaee, Salamzadeh, Shokouhi, Sahraei, The study of vitamin D administration effect on CRP and Interleukin-6 as prognostic biomarkers of ventilator associated pneumonia, J Crit Care
Mitchell, Vitamin-D and COVID-19: do defi cient risk a poorer outcome?, Lancet Diabetes Endocrinol, doi:10.1016/S2213-8587(20)30183-2
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Late treatment
is less effective
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