Should Vitamin D Supplements be Used as Adjunct Treatment for COVID-19: A Rapid Review

Abstract

Background. Pooled data from observational studies suggest that patients with serum vitamin D levels below 30 ng/mL had an increased risk of infection and mortality from COVID-19. This rapid review aimed to determine the efficacy and safety of vitamin D as an adjunct treatment for COVID-19.
 Methods. We searched MEDLINE (PubMed) and CENTRAL up to July 18, 2021. We also searched trial registries, gray literature, and reference lists of included and excluded studies in the search as well as COVID-19 guidelines. Two reviewers independently screened titles and abstracts, collected data, and assessed for risk of bias. Meta-analysis was conducted, and an evidence profile table using GRADEpro was generated. Outcomes included were mortality, need for mechanical ventilator or progression of oxygen support, duration of mechanical ventilation, ICU admission, hospital length of stay, SARS-CoV-2 positivity at day 21, and adverse events.
 Results. We found four RCTs (3 low risk of bias and 1 high risk of bias). The sources of bias among the RCTs were unclear allocation, lack of blinding of patients, caregivers, and outcome assessors, and high drop-out rate. This rapid review found that the effects of vitamin D are inconclusive for the following outcomes: mortality (pooled RR 0.62, 95% CI [0.16 to 2.41], I2=49%; n=443, 3 RCTs, very low certainty of evidence), need for mechanical ventilator or progression of oxygen support (RR 0.52, 95% CI [0.24 to 1.13], n=237, 1 RCT, low certainty of evidence), and ICU admission (pooled RR 0.37, 95% CI [0.09 to 1.61], I2=78%; n=443, 3 RCTs, very low certainty of evidence. No significant reduction in hospital length of stay was found among those treated with vitamin D (MD 0 days, 95% CI [-1.19 to 1.09], low certainty of evidence). The duration of mechanical ventilation was also was also not significantly shortened in the treatment group (15 days) compared with placebo (12.8 days), MD 2.2 days, 95% CI [-8.4 to 12.8], low certainty of evidence. Interestingly, a higher proportion of those supplemented with vitamin D showed virologic clearance for COVID-19 on day 21 (RR 3.0, 95% CI [1.26 to 7.14], n=40, 1 RCT). At dosages between 60,000 to 200,000 IU of cholecalciferol, only one episode of vomiting (0.8%) was reported.
 Conclusion. Based on the evidence found, we are uncertain whether vitamin D is beneficial or harmful for patients with COVID-19. There is very low certainty of evidence to recommend the use of vitamin D supplements as an adjunct treatment for patients with COVID-19. Vitamin D supplementation for patients with COVID-19 should be limited to clinical trials or among those with proven vitamin D deficiency. More published studies are awaited to explore the benefit or harm of vitamin D for COVID-19.