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Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis

Take Home Message

Vitamin D supplementation might be associated with improved clinical outcomes specifically ICU admission and/or mortality, in those with moderate-to-severe COVID-19 requiring hospitalization.

Results

  • 13 studies including 2933 COVID-19 patients across studies were included (10 observational studies, 3 RCTs).
  • Five studies catered to the use of vitamin D supplementation before the diagnosis of COVID-19, seven studies had reported the use of vitamin D after the diagnosis.
  • The majority of the studies had used oral cholecalciferol, 1 used oral calcifediol.
  • The dose of cholecalciferol used was highly variable across the included studies, ranging from 80,000 IU within a few hours of diagnosis of COVID-19 to a maximum of 400,000 IU supplemented as bolus oral cholecalciferol daily for 2 consecutive days (the second and third day of the in-hospital stay).
  • The pooled analysis of the data showed that the use of vitamin D supplementation was associated with improved clinical outcomes
  • A subgroup analysis was performed based on the cumulative dose of vitamin D received as per the study protocol. A cumulative dose of cholecalciferol less than 200,000 IU was categorized as a low-cumulative dose, while a dose equal to or more than 200,000 IU was classified as a high-cumulative dose. Pooled data did not show any difference in outcome in the high-cumulative dose  or low-cumulative dose subgroups . However, sensitivity analysis performed after exclusion of the RCT by Murai et al. (because they provided supplementation before and after diagnosis), showed that a high-cumulative dose of vitamin D after COVID-19 diagnosis ? was associated with improved clinical outcomes in COVID-19
  • Pooled analysis showed that vitamin D use was significantly associated with improved clinical outcomes Subgroup analysis showed that vitamin D supplementation was associated with improved clinical outcomes only in patients receiving the drug after the diagnosis of COVID-19 and not in those who had received vitamin D prior to the diagnosis
  • The present systematic review and meta-analysis shows that supplementation with vitamin D is associated with improved clinical outcomes in COVID-19, especially when vitamin D is administered in patients after the diagnosis of COVID-19.

Who

Patients diagnosed with COVID-19 requiring hospitalization.

Things to Keep in Mind

  • This analysis only included studies that assessed clinical outcomes and mortality leaving out other important clinical outcomes and or symptoms that may be related to vitamin D supplementation and or status.
  • Just like every systematic review and meta-analysis studies outside of the strict inclusion exclusion criteria are not included and thus important data may not be considered.

Author’s Conclusions

Vitamin D supplementation might be associated with improved clinical outcomes in terms of ICU admission and/or mortality, especially in those with moderate-to-severe COVID-19 requiring hospitalization. However, issues regarding the appropriate dose, duration, and mode of administration of vitamin D remain unanswered and provide avenues for further research.

Study Design

  • A systematic review and meta-analysis following PRISMS guidelines was conducted to provide a precise summary and collate the effect of vitamin D supplementation on adverse clinical outcomes in COVID-19 patients.
  • Observational studies (prospective or retrospective, cohort or case–control design) as well as randomized controlled trials, irrespective of study design (parallel/cross-over), study blinding (single-blind, double-blind, or open-label), and sample size, were included in the meta-analysis.
  • Studies included patients with COVID-19, a proportion who must have been taking vitamin D supplements prior to or after the diagnosis of COVID-19, irrespective of the dose, duration, or formulation of vitamin D used.
  • Studies included reported clinical outcomes of COVID-19 patients in terms of the need for intensive care unit (ICU) admission or mortality or both.
  • The clinical outcomes had to be reported as the rate of ICU admission/mortality (as the number of “events”) in COVID-19 patients with vitamin D supplementation compared to those who did not receive vitamin D.
  • Relevant studies where clinical outcomes were not reported in terms of ICU admission or mortality were excluded.

Reference

Pal R, Banerjee M, Bhadada SK, Shetty AJ, Singh B, Vyas A. Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis. J Endocrinol Invest. 2021 Jun 24:1–16. doi: 10.1007/s40618-021-01614-4. Epub ahead of print. PMID: 34165766; PMCID: PMC8223190.

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Research Summaries

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2021-11-02T09:57:44-05:00