Vitamin D Deficiency and Comorbidities as Risk Factors of COVID-19 Infection: A Systematic Review and Meta-analysis

Abstract

Objectives: Extensive evidence links low vitamin D status and comorbidities with coronavirus disease 2019 (COVID-19) outcomes, but the results of published studies are contradictory. Therefore, we investigated the association of lower levels of vitamin D and comorbidities with the risk of COVID-19 infection.Methods: We searched MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for articles published until August 20, 2021. Sixteen eligible studies were identified (386 631 patients, of whom 181 114 were male). We included observational cohort and case-control studies that evaluated serum levels of vitamin D in COVID-19-positive and COVID-19-negative patients. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated.Results: Significantly lower vitamin D levels were found in COVID-19-positive patients (MD, -1.70; 95% CI, -2.74 to -0.66; <i>p</i>=0.001), but with variation by study design (case-control: -4.04; 95% CI, -5.98 to -2.10; <i>p</i><0.001; cohort: -0.39; 95% CI, -1.62 to 0.84; <i>p</i>=0.538). This relationship was more prominent in female patients (MD, -2.18; 95% CI, -4.08 to -0.28; <i>p</i>=0.024) than in male patients (MD, -1.74; 95% CI, -3.79 to 0.31; <i>p</i>=0.096). Male patients showed higher odds of having low vitamin D levels (odds ratio [OR], 2.09; 95% CI, 1.38 to 3.17; <i>p</i><0.001) than female patients (OR, 1.17; 95% CI, 0.74 to 1.86; <i>p</i>=0.477). Comorbidities showed inconsistent, but generally non-significant, associations with COVID-19 infection.Conclusions: Low serum vitamin-D levels were significantly associated with the risk of COVID-19 infection. This relationship was stronger in female than in male COVID-19 patients. Limited evidence was found for the relationships between comorbidities and COVID-19 infection, warranting large population-based studies to clarify these associations.

Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials

“…At the same time, comorbidities, such as age over 65 years old, diabetes mellitus, obesity and hypertension, are important risk factors that may cause severe COVID-19 infection. A meta-analysis showed that obese patients were at a higher risk of contracting COVID-19 infection [50]. In our meta-analysis, a study involving people above 65 years of age who were supplemented with different single doses of cholecalciferol [26] detected the highest risk of death associated with COVID-19, while a study of participants who were less than 18 years old, among whom none had a normal serum levels of 25(OH)D [31], showed the lowest risk of COVID-19 mortality.…”

Self-Reported Pre-Pandemic Physical Activity and Likelihood of COVID-19 Infection: Data from the First Wave of the CoCo-Fakt Survey

“…To date, most studies have focused on the association between comorbidities and patients’ COVID-19 outcomes. For example, a systematic review and meta-analysis included 16 studies investigating various comorbidities as potential risk factors for an infection [ 31 ]. The results indicated only obesity as a risk factor; schizophrenia, dementia, and coronary heart disease resulted in lower odds of infection.…”

Mechanistic Insight into the role of Vitamin D and Zinc in Modulating Immunity Against COVID-19: A View from an Immunological Standpoint

“…About 65% of the COVID-19 patients showed hypovitaminosis D (less than 20 ng/mL) and elevated levels of the C-reactive protein, interleukin-6, tumor necrosis factor-α, d-dimers, and interleukin-10 markers. An inverse correlation was observed between the inflammatory biomarkers and the levels of 25 OH vitamin D, showing the importance of vitamin D as a marker in disease management strategies [88,89]. There has been a steady rise in research establishing vitamin D as an immunomodulator.…”