COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta–analysis of randomized controlled trials.

Vitamin D use was associated with significant decrease in rates of COVID-19-related events when all the outcomes were pooled across all RCTs.

• 6 RCTs including 551 COVID-19 subjects aged 35-56.
• When all the observations on all reported outcomes were pooled, there was statistically significant evidence on the use of vitamin D treatment in reducing overall COVID-19-related outcomes.
• The collective evidence showed that vitamin D treatment was significantly associated with reduced risk of COVID-19 severity when six observations on the number of events for symptom severity, ICU care, and mechanical ventilation were pooled.
• The pooled estimate from four studies showed that the use of vitamin D was not significantly associated with ICU outcome alone.
• COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events, and RT-PCR positivity.

6 RCTs including 551 adult subjects aged 35-56 yrs reporting the use of vitamin D intervention to control/placebo group in COVID-19.

• There were only two placebo-controlled trials, one double-blind study that used a single high dose of vitamin D.  
• The criteria for sufficient and deficient vitamin D status varied across the trials.  
• The variations in the COVID-19 severity, comorbidities proportions and standard care treatment strategies could have influenced the heterogeneity and the overall result.  
• The difference in the study settings, timings, randomization, blinding, and data collection strategies could have influenced the outcomes. 
• There was no control for confounding. 
• The included studies only assessed subjects aged 35-56 and therefore can’t be generalized to other age groups. 

“In conclusion, vitamin D use was associated with significant decrease in rates of COVID-19-related events when all the outcomes were pooled across all RCTs. However, there was no significant difference observed for the relative risk of ICU admission and mortality outcomes upon vitamin D supplementation. The overall pooled results in addition to a significant decrease in the rates of RT-PCR positivity observed in this study are suggestive of the possible beneficial effects of vitamin D. These inconclusive results would indicate the need for more RCTs in support of the beneficial effect of vitamin D in COVID-19. Furthermore, it is reasonable to speculate that Vitamin D deficiency could be a proxy of other conditions, as advanced age, BMI, diabetes, liver disease, etc., all known to negatively impact on the outcome of COVID-19. Despite randomization done in the included trials, these conditions may act as confounders, and hence, the potential benefits of Vitamin D in COVID-19 has to be interpreted with caution and needs to be investigated further in large-scale studies.” 

• A meta-analysis of randomized controlled trials comparing vitamin D supplementation to placebo on one or more of the following: COVID-19 severity, ICU care, mortality events, seropositivity, and RT-PCR positivity or any other adverse events.  
• No prespecified limitations applied for dose or type of vitamin D and follow-up durations. 
• 6 databases through August 5, 2021 were searched. 

Varikasuvu SR, Thangappazham B, Vykunta A, Duggina P, Manne M, Raj H, Aloori S. COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials. Expert Rev Anti Infect Ther. 2022 Jun;20(6):907-913. doi: 10.1080/14787210.2022.2035217. Epub 2022 Feb 3. PMID: 35086394; PMCID: PMC8862170.