Low serum vitamin D level and COVID-19 infection and outcomes, a multivariate meta-analysis

Objective This study aimed to determine whether serum vitamin D is independently associated with COVID-19 infection and outcomes in patients with COVID-19. Methods We identified relevant studies by searching the PubMed, Embase, and medRxiv databases from December 2019 to October 1, 2020. Odds ratios (ORs) were pooled using random-effects models. Only reports with multivariate adjusted results were included to avoid the impact of potential confounding factors. Results A total of six studies with 377,265 patients were identified. Overall, in the categorical analysis, a low serum vitamin D level was associated with an increased risk of COVID-19 infection (OR: 1.47, 95% CI: 1.09- 1.97, I2=81%), hospitalization (OR: 1.83, 95% CI: 1.22-2.74, I2=0%), but not in-hospital death (OR: 2.73, 95% CI: 0.27-27.61). Notably, when vitamin D level was analyzed as a continuous variable, each 5 ng/ml increase in vitamin D level was not associated with any increased risk of COVID-19 infection (OR: 1.04, 95% CI: 0.96-1.12, I2=74%) or in-hospital death (OR: 1.02, 95% CI: 0.93-1.12). Conclusions Low serum vitamin D is associated with an increased risk of COVID-19 infection and hospitalization. In-hospital death showed a tendency to be increased in COVID-19 patients with low vitamin D levels. The ongoing clinical trials for evaluation of vitamin D supplementation will be key to the validation of this adjunctive treatment for COVID-19 patients.