Impact of chronic cholecalciferol supplementation and vitamin D status on risk of post-vaccination SARS-CoV-2 breakthrough infection
et al., Endocrine, doi:10.1007/s12020-026-04677-6, NCT06452082, Jun 2026
Vitamin D for COVID-19
8th treatment shown to reduce risk in
October 2020, now with p < 0.00000000001 from 137 studies, recognized in 18 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,600+ studies for
220+ treatments. c19early.org
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Retrospective 114 vaccinated outpatients showing lower risk of symptomatic COVID-19 cases with adequate vitamin D status and cholecalciferol supplementation (similar point estimate for the full and matched population, but without statistical significance in the smaller matched population).
This is the 138th COVID-19 controlled study for vitamin D, which collectively show efficacy with p<0.0000000001.
41 studies are RCTs, which show efficacy with p=0.00000049.
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risk of symptomatic case, 50.0% lower, RR 0.50, p = 0.12, treatment 7 of 39 (17.9%), control 14 of 39 (35.9%), NNT 5.6, matched population.
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risk of symptomatic case, 49.7% lower, RR 0.50, p = 0.04, treatment 12 of 70 (17.1%), control 15 of 44 (34.1%), NNT 5.9, all patients.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
di Filippo et al., 10 Jun 2026, retrospective, Italy, peer-reviewed, 5 authors, study period January 2021 - December 2021, trial NCT06452082 (history).
Contact: giustina.andrea@hsr.it.
Abstract: ## BRIEF REPORT
Impact of chronic cholecalciferol supplementation and vitamin D status on risk of post-vaccination SARS-CoV-2 breakthrough infection
Luigi di Filippo 1 · Simona Bolamperti 1 · Marco Campaniolo 1 · Licia Gifuni 1 · Andrea Giustina 1
Received: 22 March 2026 / Accepted: 18 May 2026 © The Author(s) 2026
Abstract
Introduction Vitamin D has been implicated in modulating immune responses to COVID-19 and anti-SARS-CoV-2 vac -cination. However, whether chronic cholecalciferol supplementation influences the risk of post-vaccination breakthrough infection remains unclear. This retrospective observational study investigated the role of chronic vitamin D supplementation and circulating 25(OH) vitamin D concentrations on SARS-CoV-2 breakthrough infection after mRNA vaccination.
Methods Adult patients vaccinated with two doses of BNT162b2 and without prior SARS-CoV-2 infection were included. Individuals chronically supplemented with cholecalciferol were compared with non-supplemented subjects and subsequently matched 1:1 for age, sex, and comorbidities. Breakthrough infection within 12 months after vaccination was recorded.
Results A total of 114 patients were evaluated; 70 (61.4%) received chronic cholecalciferol supplementation and 27 (23.7%) developed breakthrough infection. Infection occurred less frequently among supplemented patients (17% vs. 34%, p = 0.044). Circulating 25(OH) vitamin D concentrations were significantly lower in patients with infection ( p < 0.001) and showed a significant predictive performance (AUROC 75.6%, p < 0.001), with an optimal cut-off of 18.5 ng/mL. In multivariable analysis, 25(OH) vitamin D concentrations emerged as the only independent predictor of breakthrough infection (OR 0.86, p = 0.003). In the matched cohort ( n = 78), breakthrough infection remained numerically lower among supplemented indi -viduals (18% vs. 36%, p = 0.125); lower 25(OH) vitamin D concentrations were independently associated with infection risk (OR 0.88, p = 0.007), with similar ROC performance (AUROC 77%, p < 0.001).
Conclusions Adequate vitamin D status, predominantly achieved through chronic cholecalciferol supplementation, was independently associated with reduced risk of SARS-CoV-2 breakthrough infection after vaccination. Maintaining sufficient 25(OH) vitamin D concentrations may represent a simple and potentially relevant strategy to optimize post-vaccination protection.
Keywords Vitamin D · vaccination · COVID-19 · cholecalciferol · SARS-CoV-2 · anti-COVID-19 vaccine
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