Second Vitamin D clinical trial, positive results

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

It has been observed that vitamin D-deficient individuals

have increased COVID-19 risk and mortality

Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA 2020;323:1824–36. doi: 10.1001/jama.2020.6019

The role of vitamin D in the prevention of coronavirus disease infection and mortality.

Aging Clin Exp Res 2020;32:1195–8. doi: 10.1007/s40520-020-01570-8

Association of vitamin D status and other clinical characteristics with COVID-19 test results.

JAMA Netw Open 2020;3:e2019722. (Published 3 Sep 2020).doi: 10.1001/jamanetworkopen.2020.19722

Immunomodulatory role and protective effect of vitamin D against other viral infections

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;15:356:i6583. doi: 10.1136/bmj.i6583

An intervention study with calcifediol noticed a reduction in requirement for intensive care among hospitalised patients for COVID19

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 2020;203:105751. doi: 10.1016/j.jsbmb.2020.105751

50 patients treated with calcifediol, one required admission to the ICU (2%), no deaths

26 untreated patients, 13 required admission (50 %) to the ICU, 2 deaths

Immune-modulatory effect of vitamin D is likely to be observed at 25(OH)D levels, which are considered higher than that required for its skeletal effects

Vitamin D to prevent COVID-19: recommendations for the design of clinical trials. Febs J2020;287:3689–92. doi: 10.1111/febs.15534

Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults.

BMC Res Notes 2012;5:575. doi: 10.1186/1756-0500-5-575

Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection.

PLoS One 2020;15:e0239799.doi: 10.1371/journal.pone.0239799

Aim

Effect of high dose, oral cholecalciferol supplementation on SARS-CoV-2 viral clearance

First cholecalciferol intervention study for asymptomatic and mildly symptomatic SARS-CoV-2 positive individuals

Design

Randomised, placebo-controlled.

Participants

Asymptomatic or mildly symptomatic SARS-CoV-2

RNA positive vitamin D deficient (25(OH) D less than 20 ng/ml)

Calcifediol, calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D3

Pre intervention baseline serum 25(OH) D

Intervention group, 8.6 ng/ml

Control group, 9.54 ng/ml (p=0.730)

10 out of 16 patients could achieve 25(OH)D more than 50 ng/ml by

day-7

Another two by day-14

Outcome measure

Proportion of patients with SARS-CoV-2 RNA negative before day-21

Change in inflammatory markers

Intervention group (n=16)

60 000 IU of cholecalciferol (oral nano-liquid droplets) for 7 days

Therapeutic target 25(OH)D more than 50 ng/ml

Cholecalciferol supplementation was continued for those with 25(OH)D less than 50 ng/ml

Fibrinogen levels significantly decreased with cholecalciferol supplementation

10 (62.5%) participants became SARS-CoV-2 RNA negative

Control group (n=24)

Placebo

5 (20.8%) participants became SARS-CoV-2 RNA negative (p less than 0.018)

Both groups

Patients requiring invasive ventilation or with significant comorbidities were excluded

25(OH)D levels were assessed at day 7

Regular measurements of: SARS-CoV-2 RNA, fibrinogen, D-dimer, procalcitonin, CRP, ferritin

Improvements

Calcifediol would have been better

Little and often for prevention