Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs

Abstract Background The associations between vitamin D and coronavirus disease 2019 (COVID-19) infection and clinical outcomes are controversial. The efficacy of vitamin D supplementation in COVID-19 is also not clear. Methods We identified relevant cohort studies that assessed the relationship between vitamin D, COVID-19 infection and associated death and randomized controlled trials (RCTs) that reported vitamin D supplementation on the outcomes in patients with COVID-19 by searching the PubMed, EMBASE, and medRxiv databases up to June 5th, 2021. Evidence quality levels and recommendations were assessed using the GRADE system. Results Eleven cohort studies with 536,105 patients and two RCTs were identified. Vitamin D deficiency (< 20 ng/ml) or insufficiency (< 30 ng/ml) was not associated with an significant increased risk of COVID-19 infection (OR for < 20 ng/ml: 1.61, 95% CI: 0.92–2.80, I2 = 92%) or in-hospital death (OR for < 20 ng/ml: 2.18, 95% CI: 0.91–5.26, I2 = 72%; OR for < 30 ng/ml: 3.07, 95% CI: 0.64–14.78, I2 = 66%). Each 10 ng/ml increase in serum vitamin D was not associated with a significant decreased risk of COVID-19 infection (OR: 0.92, 95% CI: 0.79–1.08, I2 = 98%) or death (OR: 0.65, 95% CI: 0.40–1.06, I2 = 79%). The overall quality of evidence (GRADE) for COVID-19 infection and associated death was very low. Vitamin D supplements did not significantly decrease death (OR: 0.57, I2 = 64%) or ICU admission (OR: 0.14, I2 = 90%) in patients with COVID-19. The level of evidence as qualified using GRADE was low. Conclusions Current evidence suggested that vitamin D deficiency or insufficiency was not significantly linked to susceptibility to COVID-19 infection or its associated death. Vitamin D supplements did not significantly improve clinical outcomes in patients with COVID-19. The overall GRADE evidence quality was low, we suggest that vitamin D supplementation was not recommended for patients with COVID-19