Impact of chronic cholecalciferol supplementation and vitamin D status on risk of post-vaccination SARS-CoV-2 breakthrough infection

di Filippo et al., Endocrine, doi:10.1007/s12020-026-04677-6, NCT06452082, Jun 2026
Symp. case, matched 50% improvement lower risk ← → higher risk Symp. case, all 50% Vitamin D  di Filippo et al.  PROPHYLAXIS Is prophylaxis with vitamin D beneficial for COVID-19? Retrospective 114 patients in Italy (January - December 2021) Fewer symptomatic cases with vitamin D (not stat. sig., p=0.12) c19early.org di Filippo et al., Endocrine, June 2026 0 0.5 1 1.5 2+ RR
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
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.
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.
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.
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.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org June 2026 Italy Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines Vietnam Japan Nepal China Uzbekistan Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea Saudi Arabia Algeria Morocco Yemen Poland India Venezuela DR Congo Madagascar Thailand Uganda Egypt Nigeria Taiwan Zambia Bolivia Fiji Bosnia-Herzegovina Jordan Georgia Switzerland Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Trinidad and Tobago Mongolia Czechia Israel Belarus North Macedonia Hong Kong Qatar Panama Serbia CAR Syria Italy favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org June 2026 Italy Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines Vietnam Japan Nepal China Uzbekistan Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea Saudi Arabia Algeria Morocco Yemen Poland India Venezuela DR Congo Madagascar Thailand Uganda Egypt Nigeria Taiwan Zambia Bolivia Fiji Jordan Georgia Switzerland Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore Iceland New Zealand Mongolia Czechia Israel Belarus North Macedonia Hong Kong Qatar Panama Serbia CAR Italy favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
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 &lt; 0.001) and showed a significant predictive performance (AUROC 75.6%, p &lt; 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 &lt; 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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Published 2018 Oct 12. https://doi.org/10.1530/EJE-18-0151" }, { "DOI": "10.1007/s12020-023-03551-z", "author": "L di Filippo", "doi-asserted-by": "publisher", "first-page": "342", "issue": "2", "journal-title": "Endocrine", "key": "4677_CR30", "unstructured": "L. di Filippo, F.M. Ulivieri, R. Nuti, A. Giustina, Use of vitamin D with anti-osteoporotic drugs: are available clinical trials telling us the whole story? Endocrine. 83(2), 342–348 (2024). https://doi.org/10.1007/s12020-023-03551-z", "volume": "83", "year": "2024" }, { "DOI": "10.1002/jbm4.10232", "author": "P Lips", "doi-asserted-by": "publisher", "first-page": "e10232", "issue": "1", "journal-title": "JBMR Plus", "key": "4677_CR31", "unstructured": "P. Lips, J.P. Bilezikian, R. Bouillon, D. Vitamin, Giveth to Those Who Needeth. JBMR Plus. 4(1), e10232 (2019). Published 2019 Nov 14. https://doi.org/10.1002/jbm4.10232", "volume": "4", "year": "2019" } ], "reference-count": 31, "references-count": 31, "relation": {}, "resource": { "primary": { "URL": "https://link.springer.com/10.1007/s12020-026-04677-6" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Impact of chronic cholecalciferol supplementation and vitamin D status on risk of post-vaccination SARS-CoV-2 breakthrough infection", "type": "journal-article", "update-policy": "https://doi.org/10.1007/springer_crossmark_policy", "volume": "91" }
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