Correlation between Baseline 25(OH) Vitamin D Levels and Both Humoral Immunity and Breakthrough Infection Post-COVID-19 Vaccination

Abstract

Objective: Vaccines against COVID-19 induce specific antibodies whose titer is perceived as a reliable correlate of protection. Vitamin D confers complex regulatory effects on the innate and adaptive immunity. In this study, we explored a plausible impact of baseline vitamin D content on achieved immunity following COVID-19 vaccination. Methods: A retrospective observational study comprising 73,254 naïve subjects insured by the Leumit Health Service HMO, who were vaccinated between 1 February 2020 and 30 January 2022, with one available vitamin D level prior to vaccination, was performed. The association between 25(OH) vitamin D levels, SARS-COV-2 antibody titer, and post-vaccination PCR results were evaluated. Results: Of the study population, 5026 (6.9%) tested positive for COVID-19. The proportion of low 25(OH)D levels (<30 ng/mL) was significantly higher in the PCR-positive group (81.5% vs. 79%, p < 0.001). Multivariate analysis showed a higher incidence of breakthrough infection among non-smokers [1.37 (95%CI 1.22–1.54, p< 0.001)] and lower incidences among subjects with sufficient 25(OH)D levels (>30 ng/mL) [0.87 (95%CI 0.79–0.95, p—0.004)], hyperlipidemia [0.84 (95%CI 0.76–0.93, p< 0.001], depression [OR-0.87 (95%CI: 0.79–0.96, p< 0.005], socio-economic status >10 [0.67 (95%CI 0.61–0.73, p< 0.001)], and age >44 years. SARS-COV-2 antibody titers were available in 3659 vaccinated individuals. The prevalence of antibody titers (<50 AU) among PCR-positive subjects was 42% compared to 28% among PCR-negative subjects (p < 0.001). Baseline 25(OH)D levels showed an inverse relation to total antibody titers. However, no association was found with an antibody titer <50 AU/mL fraction. Conclusion Baseline 25(OH)D levels correlated with the vaccination-associated protective COVID-19 immunity. Antibody titers < 50 AU/mL were significantly linked to breakthrough infection but did not correlate with 25(OH)D levels.

Unveiling the micronutrient‐immunity puzzle in inactivated COVID‐19 vaccination: A comprehensive analysis of circulating micronutrient levels and humoral responses in healthy adults

“…Unlike iron and zinc, serum concentrations of fat-soluble vitamins (A, D, and E) in our study displayed no significant association with either vaccine-specific antibody binding affinity or neutralizing ability against SARS-CoV-2 virus. This aligns with some existing research on COVID-19 vaccination,[21][22][23][24][25] but contrasts with others reporting positive associations between vitamin D and antibody responses [18][19][20]. These discrepancies might stem from variations in study populations, including pre-existing vitamin D status, vaccination schedules (primer vs. booster dose), vaccine type (inactivated vs. mRNA), and even participant age 23,24.…”

“…[14][15][16] Nine studies have reported the associations between serum vitamin D concentrations or status (sufficient, deficient, or insufficient) and humoral responses following COVID-19 vaccinations, yet inconsistent conclusions have been reached. [17][18][19][20][21][22][23][24][25] Investigations into the influence of micronutrients on antibody binding affinity and neutralizing capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), crucial parameters for immune protection, are virtually non-existent.…”

“…Only a limited number of studies with sample sizes ranging from 97 to 73 254 participants have investigated the associations between circulating concentrations of micronutrients, particularly those involved in immune regulation, and humoral immune responses as well as protection following inoculation with COVID-19 vaccines. [14][15][16][17][18][19][20][21][22][23][24][25] Three studies have reported no association between serum iron or selenium status, as well as concentrations of total zinc, and antibody concentrations or titers in response to COVID-19 vaccinations. [14][15][16] Nine studies have reported the associations between serum vitamin D concentrations or status (sufficient, deficient, or insufficient) and humoral responses following COVID-19 vaccinations, yet inconsistent conclusions have been reached.…”

SARS-CoV-2 Infection-Blocking Immunity Post Natural Infection: The Role of Vitamin D

“…The missing pieces of the puzzle within the complex framework of natural immunity are cellular immunity and other antibody types targeting multiple epitopes. In this regard, T cells seem to possess a pivotal role in SARS-CoV-2 protective immunity [ 38 , 39 ]. The advantage of targeting different immunogenic epitopes other than the spike protein during natural infection was reported before [ 40 , 41 ]; hence, targeting other immutable components of the viral structure, or multiple parts of the virus are emerging exciting avenues for vaccine optimization.…”

Active Vitamin D analog and SARS-CoV-2 IgG after BNT162b2 vaccination in patients with hemodialysis

“…In addition, some studies have reported that native vitamin D supplementation protects against infectious diseases, particularly respiratory diseases 20 . In research on SARS-CoV-2 vaccination studies, several reports showed the association between 25OHD levels and SARS-CoV-2 IgG titers 21,22 . These studies reported that higher 25OHD levels were associated with higher SARS-CoV-2 IgG after vaccination.…”