Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis

Vitamin D supplementation had no significant impact on the risk of COVID-19 infection, whereas it showed protective effects against mortality and ICU admission in hospitalized COVID-19 patients. 

• 23 studies were included, 9 RCTS and 14 NRIS.
• Five studies were identified (one RCT, four NRISs) on primary prevention, with five (two RCTs, three NRISs) on secondary prevention, and 13 (six RCTs, seven NRISs) on tertiary prevention. 
• Pooled analysis showed no significant effect on the risk of COVID-19 infection. No meta-analysis was possible on hospitalization risk due to paucity of data.
• Vitamin D supplementation was significantly associated with a reduced risk of ICU admission and mortality.

Studies assessing vitamin D in adults with COVID-19.

• There was a lot of variation in study design among the studies included 
• The authors of this meta–analysis could not speak to the control of confounding in the individual studies 
• Studies include adults only 

Our findings suggest that vitamin D supplementation, administered in hospitalized COVID-19 patients, is associated with a significant reduction in mortality, ICU admission, and need for mechanical ventilation. Nevertheless, uncertainty remains on the characteristics of individuals with stronger protective effects and the type of intervention (e.g., dose, regimen, duration) yielding the greatest benefit. There was insufficient evidence to determine whether vitamin D supplementation can significantly decrease the risk of acquiring COVID-19 infection when taken as a primary prevention or reduce the severity and risk of hospital admission when taken as secondary prevention in asymptomatic or mildly symptomatic COVID-19 cases. An updated meta-analysis upon completion of ongoing trials is needed to expand our understanding of the effects of vitamin D supplementation on preventing and managing COVID-19.

• A systematic search of relevant papers published until January 2022 was conducted to identify randomized controlled trials (RCTs) and non-randomized studies of intervention (NRISs). 
• Search Strategy A systematic search of relevant papers published until January 2022 was conducted using PubMed, Cochrane, CINAHL, and EMBASE. The search strategy was based on the following Medical Subject Headings search terms: (vitamin D OR cholecalciferol OR ergocalciferol OR 1,25(OH)D OR 25(OH)D, *cholecalciferol OR Calcifediol OR calcitriol OR *Dihydroxyvitamin D3 OR *D3 OR *D2) AND (COVID-19 OR SARS-CoV-2 OR coronavirus OR Coronaviridae OR Severe Acute Respiratory Distress Syndrome OR Severe acute respiratory syndrome coronavirus OR cytokine releasing syndrome OR cytokine storm). We searched clinicaltrials.gov, up until January 2022, for recently completed trials on vitamin D and COVID-19 and contacted authors to inquire about publication status. The reference lists of retrieved articles, systematic reviews, review articles, and clinical trial registration websites were also searched to identify other relevant studies. 
• Studies were eligible if they were randomized RCTs or NRISs, that is, quasi-experimental studies, cohorts, and case–control studies, testing the impact of vitamin D supplementation, with no time restriction. 
• Study participants were people of all ages, genders, or ethnicities who were either non-infected (primary prevention) or infected (secondary and tertiary prevention) with SARS-CoV-2. 
• The intervention was supplementation of vitamin D provided in any dose, format (oral vs. non-oral), or frequency (bolus, daily, weekly, etc.). Subjects who received vitamin D supplementation comprised the intervention arm, whereas those who received placebo or no vitamin D supplementation constituted the control arm. Standard therapy was permitted as a co-intervention, if provided to both groups. 
• The primary outcome for studies pertaining to primary prevention was COVID-19 incidence, defined as a positive SARS-CoV-2 infection.

Hosseini B, El Abd A, Ducharme FM. Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients. 2022 May 20;14(10):2134. doi: 10.3390/nu14102134. PMID: 35631275; PMCID: PMC9147949.