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Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)
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  1. Ashu Rastogi1,
  2. Anil Bhansali1,
  3. Niranjan Khare2,
  4. Vikas Suri2,
  5. Narayana Yaddanapudi3,
  6. Naresh Sachdeva1,
  7. G D Puri3,
  8. Pankaj Malhotra2
  1. 1 Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
  2. 2 Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
  3. 3 Anaesthesia, Post Graduate Institute of Medical Education and Research, Chandigarh, India
  1. Correspondence to Pankaj Malhotra, Department Of Internal Medicine, Nehru Hospital, PGIMER, Chandigarh 160012, India; malhotrapankaj{at}hotmail.com

Abstract

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.

  • Infectious diseases
  • Virology
  • Diabetes & endocrinology

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Footnotes

  • All the authors had access to the data and were involved in writing the manuscript as per ICMJE criteria.

  • Contributors AR and AB conceived the study, designed the study protocol. AR analysed the data and wrote the initial draft of the manuscript. NK, VS, NY, GDP and PM were involved in clinical care of the participants. VS, NY, AB and PM edited the final draft of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • 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 peer-reviewed. 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.

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