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

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.

• 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.

Patients diagnosed with COVID-19 requiring hospitalization.

• 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.

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.

• 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.

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.