Association of vitamin D deficiency with COVID‐19 infection severity: Systematic review and meta‐analysis

Abstract

Background We sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID‐19) infection. Methods Multiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID‐19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission. Results Seventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50–4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40–7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48–3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25–0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut‐offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends. Conclusions Vitamin D deficiency is associated with greater severity of COVID‐19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID‐19.

Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients

“…More relevant to the present study, one meta-analysis concluded that there was a non-significant trend between low 25OHD levels (below 20 ng/ml) and need for ICU admission, length of hospital stay or mortality 12 . The other meta-analysis with a greater restriction of high-quality studies, which included 2,756 patients, found a significantly higher mortality (OR: 2.47, 95% CI: 1.50 to 4.05), higher rates of hospital admissions (OR: 2.18, IC del 95%: 1.48–3.21 and longer hospital stay in subjects with the poorest vitamin D status 13 .…”

“…Thereafter, several studies evaluated the association between vitamin D status and risk or severity of SARS-CoV-2 infection 4 – 9 . Two recent meta-analyses have looked at published data linking vitamin D status with the risk or severity (ICU admission and mortality) of COVID-19 infections 12 , 13 . Probably related to the selection of studies they came to different conclusions, as one meta-analysis 12 found an uncertain trend and the other 13 a significantly increased risk of infection in subjects with the poorest vitamin D status.…”

“…Two recent meta-analyses have looked at published data linking vitamin D status with the risk or severity (ICU admission and mortality) of COVID-19 infections 12 , 13 . Probably related to the selection of studies they came to different conclusions, as one meta-analysis 12 found an uncertain trend and the other 13 a significantly increased risk of infection in subjects with the poorest vitamin D status. More relevant to the present study, one meta-analysis concluded that there was a non-significant trend between low 25OHD levels (below 20 ng/ml) and need for ICU admission, length of hospital stay or mortality 12 .…”

“…Several Mendelian Randomization studies demonstrated that genetically low serum 25OHD concentrations increase the risk of multiple sclerosis 2 and a meta-analysis found a reduced incidence of upper respiratory infections when supplements of vitamin D are given to relatively vitamin D deficient subjects 3 . There are now multiple association studies 4 – 10 and meta-analyses 11 – 13 linking a poor vitamin D status with increased risk 4 , 8 – 10 or severity of COVID-19 infections 4 – 7 .…”

El rol de la suplementación con vitamina D en la infección por COVID-19

“…Si bien existe consenso en la comunidad científica acerca de que no se ha establecido una clara relación causal entre los valores de vitamina D y el COVID-19 15,16 , el interés creciente en este tema se refleja en los hallazgos de nuestra estrategia de búsqueda, mediante la cual encontramos numerosas revisiones sistemáticas publicadas en los primeros meses de este año dirigidas a evaluar las infecciones por SARS-CoV-2 en relación con los niveles séricos de esta vitamina [17][18][19][20][21][22][23][24][25][26][27][28] . A pesar de que la mayoría de ellas concluye que niveles bajos de esta biomolécula podrían estar asociados con un mayor riesgo de COVID-19 o con el desarrollo de formas más severas de la enfermedad, la confianza en esta evidencia es muy baja, por provenir de estudios observacionales, con alta heterogeneidad clínica y metodológica y riesgo de sesgo de publicación significativo, por lo que no es suficiente para avalar un efecto terapéutico o preventivo de la administración de suplementos de esta vitamina.…”