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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Viral clearance 53% Improvement Relative Risk Vitamin D  SHADE  LATE TREATMENT  RCT Is late treatment with vitamin D beneficial for COVID-19? RCT 40 patients in India Improved viral clearance with vitamin D (p=0.018) c19early.org Rastogi et al., Postgraduate Medical J., Nov 2020 Favors vitamin D Favors control

Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)

Rastogi et al., Postgraduate Medical Journal, doi:10.1136/postgradmedj-2020-139065, SHADE, NCT04459247
Nov 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 118 studies, recognized in 7 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments. c19early.org
53% reduction in PCR+ with high-dose cholecalciferol supplementation. RCT with 16 treatment patients and 24 control patients. 25(OH)D levels at day 14 were 52 ng/ml vs. 15 ng/ml in the intervention and control group.
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.
This is the 2nd of 29 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000035.
This is the 11th of 118 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 30 sextillion).
risk of no viral clearance, 52.6% lower, RR 0.47, p = 0.02, treatment 6 of 16 (37.5%), control 19 of 24 (79.2%), NNT 2.4.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Rastogi et al., 12 Nov 2020, Randomized Controlled Trial, India, peer-reviewed, 8 authors, dosage 60,000IU days 1-7, trial NCT04459247 (history) (SHADE).
This PaperVitamin DAll
Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)
Ashu Rastogi, Anil Bhansali, Niranjan Khare, Vikas Suri, Narayana Yaddanapudi, Naresh Sachdeva, G D Puri, Pankaj Malhotra
Postgraduate Medical Journal, doi:10.1136/postgradmedj-2020-139065
Background Vitamin D has an immunomodulatory role but the effect of therapeutic vitamin D supplementation in SARS-CoV-2 infection is not known. Aim Effect of high dose, oral cholecalciferol supplementation on SARS-CoV-2 viral clearance. Design Randomised, placebo-controlled. Participants Asymptomatic or mildly symptomatic SARS-CoV-2 RNA positive vitamin D deficient (25(OH) D<20 ng/ml) individuals. Intervention Participants were randomised to receive daily 60 000 IU of cholecalciferol (oral nano-liquid droplets) for 7 days with therapeutic target 25(OH) D>50 ng/ml (intervention group) or placebo (control group). Patients requiring invasive ventilation or with significant comorbidities were excluded. 25(OH)D levels were assessed at day 7, and cholecalciferol supplementation was continued for those with 25(OH)D <50 ng/ml in the intervention arm. SARS-CoV-2 RNA and inflammatory markers fibrinogen, D-dimer, procalcitonin and (CRP), ferritin were measured periodically. Outcome measure Proportion of patients with SARS-CoV-2 RNA negative before day-21 and change in inflammatory markers. Results Forty SARS-CoV-2 RNA positive individuals were randomised to intervention (n=16) or control (n=24) group. Baseline serum 25(OH)D was 8.6 (7.1 to 13.1) and 9.54 (8.1 to 12.5) ng/ml (p=0.730), in the intervention and control group, respectively. 10 out of 16 patients could achieve 25(OH)D>50 ng/ml by day-7 and another two by day-14 [day-14 25(OH)D levels 51.7 (48.9 to 59.5) ng/ml and 15.2 (12.7 to 19.5) ng/ml (p<0.001) in intervention and control group, respectively]. 10 (62.5%) participants in the intervention group and 5 (20.8%) participants in the control arm (p<0.018) became SARS-CoV-2 RNA negative. Fibrinogen levels significantly decreased with cholecalciferol supplementation (intergroup difference 0.70 ng/ml; P=0.007) unlike other inflammatory biomarkers. Conclusion Greater proportion of vitamin D-deficient individuals with SARS-CoV-2 infection turned SARS-CoV-2 RNA negative with a significant decrease in fibrinogen on high-dose cholecalciferol supplementation. Trial register number NCT04459247.
Competing interests None declared. Patient consent for publication Not required. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available upon reasonable request. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peerreviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/ or omissions arising from translation and adaptation or otherwise. This article is made freely available for use in accordance with BMJ's website terms and conditions for the duration of the COVID-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, noncommercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. What is already known on the subject ► Vitamin-D has immunomodulatory effect and may reduce susceptibility and severity of viral infections but its role in SARS-CoV-2 infection is not known. ORCID iD..
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Late treatment
is less effective
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