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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. 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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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. 38% [25‑49%] 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 16th of 115 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 30 sextillion). 27 studies are RCTs, which show efficacy with p=0.00002.
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.
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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.
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Late treatment
is less effective
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