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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 82% Improvement Relative Risk ICU admission 34% Oxygen therapy 32% Vitamin D  Jevalikar et al.  LATE TREATMENT Is late treatment with vitamin D beneficial for COVID-19? Prospective study of 197 patients in India Lower mortality (p=0.12) and ICU admission (p=0.29), not sig. c19early.org Jevalikar et al., Scientific Reports, Dec 2020 Favors vitamin D Favors control

Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19

Jevalikar et al., Scientific Reports, doi:10.1038/s41598-021-85809-y (date from preprint)
Dec 2020  
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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
Prospective study of 410 hospitalized patients in India showing lower mortality and ICU admission with cholecalciferol treatment, although not statistically significant with the small number of cases. The median total dose was 60,000IU.
No significant difference was found for outcomes based on baseline vitamin D deficiency, however this analysis does not appear to account for the deficient patients that were treated with vitamin D.
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. 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.
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 infections Griffin, Martineau. 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 activation Griffin.
This is the 16th 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, 82.0% lower, RR 0.18, p = 0.12, treatment 1 of 128 (0.8%), control 3 of 69 (4.3%), NNT 28.
risk of ICU admission, 33.7% lower, RR 0.66, p = 0.29, treatment 16 of 128 (12.5%), control 13 of 69 (18.8%), NNT 16.
risk of oxygen therapy, 31.7% lower, RR 0.68, p = 0.06, treatment 38 of 128 (29.7%), control 30 of 69 (43.5%), NNT 7.3.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Jevalikar et al., 28 Dec 2020, prospective, India, peer-reviewed, 8 authors, dosage 60,000IU single dose, median total dose.
This PaperVitamin DAll
Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19
Ganesh Jevalikar, Ambrish Mithal, Anshu Singh, Rutuja Sharma, Khalid J Farooqui, Shama Mahendru, Arun Dewan, Sandeep Budhiraja
Scientific Reports, doi:10.1038/s41598-021-85809-y
Vitamin D deficiency (VDD) owing to its immunomodulatory effects is believed to influence outcomes in COVID-19. We conducted a prospective, observational study of patients, hospitalized with COVID-19. Serum 25-OHD level < 20 ng/mL was considered VDD. Patients were classified as having mild and severe disease on basis of the WHO ordinal scale for clinical improvement (OSCI). Of the 410 patients recruited, patients with VDD (197,48.2%) were significantly younger and had lesser comorbidities. The levels of PTH were significantly higher in the VDD group (63.5 ± 54.4 vs. 47.5 ± 42.9 pg/mL). The proportion of severe cases (13.2% vs.14.6%), mortality (2% vs. 5.2%), oxygen requirement (34.5% vs.43.4%), ICU admission (14.7% vs.19.8%) was not significantly different between patients with or without VDD. There was no significant correlation between serum 25-OHD levels and inflammatory markers studied. Serum parathormone levels correlated with D-dimer (r 0.117, p-0.019), ferritin (r 0.132, p-0.010), and LDH (r 0.124, p-0.018). Amongst VDD patients, 128(64.9%) were treated with oral cholecalciferol (median dose of 60,000 IU). The proportion of severe cases, oxygen, or ICU admission was not significantly different in the treated vs. untreated group. In conclusion, serum 25-OHD levels at admission did not correlate with inflammatory markers, clinical outcomes, or mortality in hospitalized COVID-19 patients. Treatment of VDD with cholecalciferol did not make any difference to the outcomes.
Author contributions G.J. drafted the study protocol, supervised patient enrollment, analyzed data, wrote the first draft of the manuscript, and will be the corresponding author for the manuscript. A.M. conceptualized the study, guided the study protocol, and critically reviewed the manuscript. A.S. supervised collection and reporting of laboratory investigations and contributed to the data collection. R.S., K.J.F., S.M. contributed to the data collection and analysis. K.J.F. reviewed the study protocol. A.D., S.B. critically reviewed the manuscript along with A.M. Competing interests The authors declare no competing interests.
References
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Invest.', 'key': '85809_CR26', 'unstructured': 'Carpagnano, G. E. et al. Vitamin D deficiency as a predictor of poor ' 'prognosis in patients with acute respiratory failure due to COVID-19. J. ' 'Endocrinol. Invest. 1, 1. https://doi.org/10.1007/s40618-020-01370-x ' '(2020).', 'volume': '1', 'year': '2020'}, { 'DOI': '10.1016/j.clnu.2020.10.055', 'author': 'E Cereda', 'doi-asserted-by': 'publisher', 'first-page': '1', 'journal-title': 'Clin. Nutr.', 'key': '85809_CR27', 'unstructured': 'Cereda, E. et al. Vitamin D 25OH deficiency in COVID-19 patients ' 'admitted to a tertiary referral hospital. Clin. Nutr. 1, 1. ' 'https://doi.org/10.1016/j.clnu.2020.10.055 (2020).', 'volume': '1', 'year': '2020'}, { 'DOI': '10.1210/clinem/dgaa733', 'author': 'JL Hernández', 'doi-asserted-by': 'publisher', 'first-page': '1', 'journal-title': 'J. Clin. Endocrinol. Metab.', 'key': '85809_CR28', 'unstructured': 'Hernández, J. L. et al. Vitamin D status in hospitalized patients with ' 'SARS-CoV-2 infection. J. Clin. Endocrinol. Metab. 1, 1. ' 'https://doi.org/10.1210/clinem/dgaa733 (2020).', 'volume': '1', 'year': '2020'}, { 'DOI': '10.3390/nu12092775', 'author': 'A Pizzini', 'doi-asserted-by': 'publisher', 'first-page': '1', 'journal-title': 'Nutrients', 'key': '85809_CR29', 'unstructured': 'Pizzini, A. et al. Impact of vitamin D deficiency on COVID-19: A ' 'prospective analysis from the CovILD registry. Nutrients 12, 1. ' 'https://doi.org/10.3390/nu12092775 (2020).', 'volume': '12', 'year': '2020'}, { 'DOI': '10.1136/postgradmedj-2020-139065', 'author': 'A Rastogi', 'doi-asserted-by': 'publisher', 'first-page': '1', 'journal-title': 'Postgraduate Med. J.', 'key': '85809_CR30', 'unstructured': 'Rastogi, A. et al. Short term, high-dose vitamin D supplementation for ' 'COVID-19 disease: A randomised, placebo-controlled, study (SHADE study). ' 'Postgraduate Med. J. 1, 1. 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' 'https://doi.org/10.1001/jama.2020.26848 (2020).\xa0'}], 'reference-count': 32, 'references-count': 32, 'relation': { 'has-preprint': [ { 'asserted-by': 'object', 'id': '10.21203/rs.3.rs-129238/v1', 'id-type': 'doi'}]}, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41598-021-85809-y'}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': ['Multidisciplinary'], 'subtitle': [], 'title': 'Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality ' 'in Indian patients hospitalized for COVID-19', 'type': 'journal-article', 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'volume': '11'}
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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