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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 81% Improvement Relative Risk Vitamin D  Alcala-Diaz et al.  LATE TREATMENT Is late treatment with vitamin D beneficial for COVID-19? Retrospective 537 patients in Spain Lower mortality with vitamin D (p=0.037) c19early.org Alcala-Diaz et al., Nutrients, May 2021 Favors vitamin D Favors control

Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study

Alcala-Diaz et al., Nutrients, doi:10.3390/nu13061760
May 2021  
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Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
 
*, now known with p < 0.00000000001 from 120 studies, recognized in 8 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
Retrospective 537 patients in Spain, 79 treated with calcifediol, showing significantly lower mortality with treatment. The treated group had a higher risk of comorbidity, whereas the control group had lower O2 saturation, higher CURB-65, and higher ARDS (severity measures were included in the multivariate analysis).
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. 39% [26‑49%] 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 36th of 120 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 248 sextillion).
29 studies are RCTs, which show efficacy with p=0.0000024.
risk of death, 80.8% lower, RR 0.19, p = 0.04, treatment 4 of 79 (5.1%), control 90 of 458 (19.7%), NNT 6.9, adjusted per study, odds ratio converted to relative risk, day 30, multivariate logistic regression.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Alcala-Diaz et al., 21 May 2021, retrospective, Spain, peer-reviewed, 17 authors, dosage calcifediol 0.5mg day 1, 0.27mg day 3, 0.27mg day 7, 0.27mg day 14, 0.27mg day 21, 0.27mg day 28.
This PaperVitamin DAll
Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study
Juan F Alcala-Diaz, Laura Limia-Perez, Ricardo Gomez-Huelgas, Maria D Martin-Escalante, Begoña Cortes-Rodriguez, Jose L Zambrana-Garcia, Marta Entrenas-Castillo, Ana I Perez-Caballero, Maria D López-Carmona, Javier Garcia-Alegria, Aquiles Lozano Rodríguez-Mancheño, Maria Del Sol Arenas-De Larriva, Luis M Pérez-Belmonte, Irwin Jungreis, Roger Bouillon, Jose Manual Quesada-Gomez, Jose Lopez-Miranda
Nutrients, doi:10.3390/nu13061760
Context. Calcifediol has been proposed as a potential treatment for COVID-19 patients. Objective: To compare the administration or not of oral calcifediol on mortality risk of patients hospitalized because of COVID-19. Design: Retrospective, multicenter, open, non-randomized cohort study. Settings: Hospitalized care. Patients: Patients with laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the South of Spain. Intervention: Patients received calcifediol (25-hydroxyvitamin D 3 ) treatment (0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or not. Main Outcome Measure: In-hospital mortality during the first 30 days after admission. Results: A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol (mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving such treatment (mortality rate of 20%; p < 0.01). Patients who received calcifediol after admission were more likely than those not receiving treatment to have comorbidity and a lower rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg, and age Nutrients 2021, 13, 1760. https://doi.org/10.3390/nu13061760 https://www.mdpi.com/journal/nutrients ≥ 65 years), acute respiratory distress syndrome (moderate or severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a multivariable logistic regression model, adjusting for confounders, there were significant differences in mortality for patients receiving calcifediol compared with patients not receiving it (OR = 0.16 (95% CI 0.03 to 0.80). Conclusion: Among patients hospitalized with COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was significantly associated with lower in-hospital mortality during the first 30 days. The observational design and sample size may limit the interpretation of these findings.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Conflicts of Interest: JFAD received lecture fees from Bayer, Grunenthal Pharma, Esteve, Ferrer, and Boehringer Ingelheim outside the submitted work. LLP received lecture fees from Gebro Pharma S.A., Boehringer Ingelheim, Pfizer, Mylan, Almirall, SANOFI, and ESTEVE outside the submitted work. IJ, RGH, MDME, BCR, JLZG, MEC, AIPC, MDLC, JGA, ALRM, MDSAL, and LMPB have nothing to declare. RB received lecture fees from Abiogen, Faes Farma, Fresenius, and Proctor and Gamble outside the submitted work. JMQG received lecture fees from FAES Farma (Spain) and Amgen related to vitamin D-these activities in no way influenced the writing of the present manuscript. JLM received lecture fees from AMGEN, SANOFI, FERRER, Laboratorios Dr. Esteve, and Boehringer Ingelheim-Lilly outside the submitted work. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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{ 'DOI': '10.3390/nu13061760', 'ISSN': ['2072-6643'], 'URL': 'http://dx.doi.org/10.3390/nu13061760', 'abstract': '<jats:p>Context. Calcifediol has been proposed as a potential treatment for COVID-19 ' 'patients. Objective: To compare the administration or not of oral calcifediol on mortality ' 'risk of patients hospitalized because of COVID-19. Design: Retrospective, multicenter, open, ' 'non-randomized cohort study. Settings: Hospitalized care. Patients: Patients with ' 'laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the ' 'South of Spain. Intervention: Patients received calcifediol (25-hydroxyvitamin D3) treatment ' '(0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or ' 'not. Main Outcome Measure: In-hospital mortality during the first 30 days after admission. ' 'Results: A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median ' 'age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality ' 'during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol ' '(mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving ' 'such treatment (mortality rate of 20%; p &lt; 0.01). Patients who received calcifediol after ' 'admission were more likely than those not receiving treatment to have comorbidity and a lower ' 'rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea &gt; ' '7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure &lt; 90 mm Hg or diastolic blood ' 'pressure ≤ 60 mm Hg, and age ≥ 65 years), acute respiratory distress syndrome (moderate or ' 'severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a ' 'multivariable logistic regression model, adjusting for confounders, there were significant ' 'differences in mortality for patients receiving calcifediol compared with patients not ' 'receiving it (OR = 0.16 (95% CI 0.03 to 0.80). Conclusion: Among patients hospitalized with ' 'COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was ' 'significantly associated with lower in-hospital mortality during the first 30 days. The ' 'observational design and sample size may limit the interpretation of these findings.</jats:p>', 'alternative-id': ['nu13061760'], 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-4572-3611', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Alcala-Diaz', 'given': 'Juan F.', 'sequence': 'first'}, {'affiliation': [], 'family': 'Limia-Perez', 'given': 'Laura', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-9909-3555', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Gomez-Huelgas', 'given': 'Ricardo', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0003-1932-8682', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Martin-Escalante', 'given': 'Maria D.', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Cortes-Rodriguez', 'given': 'Begoña', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Zambrana-Garcia', 'given': 'Jose L.', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Entrenas-Castillo', 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Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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