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All Studies   Meta Analysis   Recent:  
0 0.5 1 1.5 2+ Mortality 86% Improvement Relative Risk Ventilation 80% ICU admission 38% Hospitalization time 40% Δ SaO2/FIO2 86% primary Vitamin D  Elamir et al.  LATE TREATMENT  RCT Is late treatment with vitamin D beneficial for COVID-19? RCT 50 patients in the USA (September - December 2020) Improved recovery with vitamin D (p=0.031) Elamir et al., Bone, September 2021 Favors vitamin D Favors control

A Randomized Pilot Study Using Calcitriol in Hospitalized Patients

Elamir et al., Bone, doi:10.1016/j.bone.2021.116175
Sep 2021  
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RCT 50 hospitalized patients in the USA, 25 treated with calcitriol, showing significantly improved oxygenation with treatment. Mortality, intubation, ICU admission, and hospitalization time also favored treatment, while not reaching statistical significance with the very small sample size.
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 6th of 27 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.00002.
This is the 53rd of 115 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 30 sextillion).
risk of death, 85.7% lower, RR 0.14, p = 0.23, treatment 0 of 25 (0.0%), control 3 of 25 (12.0%), NNT 8.3, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of mechanical ventilation, 80.0% lower, RR 0.20, p = 0.48, treatment 0 of 25 (0.0%), control 2 of 25 (8.0%), NNT 12, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 37.5% lower, RR 0.62, p = 0.33, treatment 5 of 25 (20.0%), control 8 of 25 (32.0%), NNT 8.3.
hospitalization time, 40.5% lower, relative time 0.60, p = 0.14, treatment 25, control 25.
relative Δ SaO2/FiO2, RR 0.14, p = 0.03, treatment 25, control 25, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Elamir et al., 8 Sep 2021, Randomized Controlled Trial, USA, peer-reviewed, 9 authors, study period September 2020 - December 2020, dosage calcitriol 0.5μg days 1-14.
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This PaperVitamin DAll
A randomized pilot study using calcitriol in hospitalized COVID-19 patients
MD Yasmine M Elamir, MD Hajira Amir, MD Steven Lim, MD Yesha Patel Rana, Carolina Gonzalez Lopez, MD Natalia Viera Feliciano, MD Ali Omar, MD William Paul Grist, MD Michael A Via
Bone, doi:10.1016/j.bone.2021.116175
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
ACKNOWLEDGEMENTS There are no acknowledgements. that were also given losartan suggests that vitamin D functions, in part, by up-regulating the pulmonary renin/angiotensin system to mitigate lung damage. (19) This same system is disrupted by COVID-19 infection. (20) Human trials with cholecalciferol therapy for ARDS have mixed results. In a randomized trial, patients that underwent esophagectomy demonstrated a transient reduction in markers of ARDS with 300,000 IU treatment of cholecalciferol compared to placebo. (21) The authors argue that declining levels of VDBP that were observed in this trial may explain the short-lived benefit of cholecalciferol that was observed. In another randomized trial of 475 mechanically ventilated ICU patients given 540,000 units cholecalciferol vs placebo, a 44% reduction in hospital mortality was observed in the cholecalciferol treated patients among the subgroup of patients with 25-hydroxyvitamin D levels less than 12 ng/ml. (22) In addition, the cholecalciferol treated patients demonstrated a further reduction in mortality that persisted for 6 months of follow up. ( 22 ) A larger, multicenter trial is currently underway. (23) Limitations of our trial include lack of a placebo and lack of blinding. It is unlikely this would affect the SaO2/FIO2 endpoint. Additionally, 25-hydroxyvitamin D levels were not measured in our study. Enrollment of patients without regard to vitamin D status strengthens the generalizability of the results...
Amrein, Parekh, Westphal, Preiser, Berghold et al., Effect of highdose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency: a study protocol of a multicentre, placebo-controlled double-blind phase III RCT (the VITDALIZE study), BMJ Open
Amrein, Schnedl, Holl, Riedl, Christopher et al., Effect of highdose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial, JAMA
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Bilezikian, Bikle, Hewison, Lazaretti-Castro, Formenti et al., MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19, Eur J Endocrinol
Castillo, Costa, Barrios, Diaz, Lopez, None
Catoire, Tellier, De La Riviere, Beauvieux, Valdenaire et al., Assessment of the SpO2/FiO2 ratio as a tool for hypoxemia screening in the emergency department, Am J Emerg Med
Dancer, Parekh, Lax, Souza, Zheng et al., Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS), Thorax
Grein, Ohmagari, Shin, Diaz, Asperges et al., Compassionate Use of Remdesivir for Patients with Severe Covid-19, N Engl J Med
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Henderson, Fink, Bassyouni, Argiropoulos, Brown et al., Vitamin D-Binding Protein Deficiency and Homozygous Deletion of the GC Gene, N Engl J Med
Hewison, Freeman, Hughes, Evans, Bland et al., Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells, J Immunol
Kong, Zhu, Shi, Liu, Chen et al., VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system, Mol Endocrinol
Laird, Rhodes, Kenny, Vitamin D and Inflammation: Potential Implications for Severity of Covid-19, Ir Med J
Lee, Eisman, Center, Vitamin D deficiency in critically ill patients, N Engl J Med
Miranda, Bouillon, Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study, J Steroid Biochem Mol Biol
Murai, Fernandes, Sales, Pinto, Goessler et al., Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial, JAMA
Nierman, Mechanick, Bone hyperresorption is prevalent in chronically critically ill patients, Chest
Parekh, Dancer, Scott, Souza, Howells et al., Vitamin D to Prevent Lung Injury Following Esophagectomy-A Randomized, Placebo-Controlled Trial, Crit Care Med
Rhodes, Dunstan, Laird, Subramanian, Kenny, COVID-19 mortality increases with northerly latitude after adjustment for age suggesting a link with ultraviolet and vitamin D, BMJ Nutr Prev Health
Santana, De Sousa, Amorim, Menezes, Araújo et al., SaO2/FiO2 ratio as risk stratification for patients with sepsis, Critical Care
Vaduganathan, Vardeny, Michel, Mcmurray, Pfeffer et al., None
Van Den Berghe, Van Roosbroeck, Vanhove, Wouters, Pourcq et al., Bone turnover in prolonged critical illness: effect of vitamin D, J Clin Endocrinol Metab
Waldron, Ashby, Cornes, Bechervaise, Razavi et al., Vitamin D: a negative acute phase reactant, J Clin Pathol
Zehnder, Bland, Williams, Mcninch, Howie et al., Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase, J Clin Endocrinol Metab
Late treatment
is less effective
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