Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis

Abstract

Background: This systematic review and meta-analysis aimed to assess whether low serum 25-hydroxyvitamin D (25-OHD) level is associated with susceptibility to COVID-19, severity, and mortality related to COVID-19.Methods: Systematic literature searches of PubMed, Scopus, and Embase database up until 9 December 2020. We include published observational prospective and retrospective studies with information on 25-OHD that reported main/secondary outcome. Low serum 25-OHD refers to participants with serum 25-OHD level below a cut-off point ranging from 20 to 30 ng/mL. Other cut-off values were excluded to reduce heterogeneity. The main outcome was mortality defined as non-survivor/death. The secondary outcome was susceptibility and severe COVID-19.Results: There were 14 studies comprising of 999,179 participants. Low serum 25-OHD was associated with higher rate of COVID-19 infection compared to the control group (OR = 2.71 [1.72, 4.29], p < 0.001; I2: 92.6%). Higher rate of severe COVID-19 was observed in patients with low serum 25-OHD (OR = 1.90 [1.24, 2.93], p = 0.003; I2: 55.3%), with a sensitivity of 83%, specificity of 39%, PLR of 1.4, NLR of 0.43, and DOR of 3. Low serum 25-OHD was associated with higher mortality (OR = 3.08 [1.35, 7.00], p = 0.011; I2: 80.3%), with a sensitivity of 85%, specificity of 35%, PLR of 1.3, NLR of 0.44, and DOR of 3. Meta-regression analysis showed that the association between low serum 25-OHD and mortality was affected by male gender (OR = 1.22 [1.08, 1.39], p = 0.002), diabetes (OR = 0.88 [0.79, 0.98], p = 0.019).Conclusion: Low serum 25-OHD level was associated with COVID-19 infection, severe presentation, and mortality.

Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis

“…As is the case with COVID-19 infection, there is ample data to suggest that vitamin D deficiency is associated with COVID-19 severity and mortality [4][5][6]33]. Although contradictory literature exists wherein the relationship between vitamin D and COVID-19 has been negated [13], several systematic reviews and meta-analyses, albeit based on observational studies, suggest a consistent negative association between serum 25-hydroxyvitamin D levels and COVID-19 disease severity [3,[34][35][36][37].…”

Dietary Behaviors and Incident COVID-19 in the UK Biobank

“…While nutrition may theoretically impact COVID-19 susceptibility [3,6,[30][31][32], few investigations have specifically tested the hypothesis a priori. Low vitamin D status is associated with COVID-19 infection, severity, and mortality [33,34]. Del Ser et al [35] recently explored a variety of risk factors for the incidence, severity, and mortality of COVID-19 in a Spanish cohort of 913 volunteers aged 75-90 years.…”

Vitamin D and Exercise Are Major Determinants of Natural Killer Cell Activity, Which Is Age- and Gender-Specific

“…Thus, vitamin D insufficiency [i.e., serum 25 (OH)D level 20-29.9 ng/mL] or deficiency [serum 25(OH)D level < 20 ng/mL] are associated with increased infection susceptibility, increased cancer incidence, poor survival of cancer patients, and development of autoimmune diseases (34,36,37). For example, recent studies suggested that vitamin D insufficiency and deficiency were associated with increased susceptibility to COVID-19 and severe presentation and mortality from it (38)(39)(40). Vitamin D, having an immune modulatory function, is considered to reduce the production of pro-inflammatory cytokines, thus, reducing the severity and mortality of COVID-19 (35).…”