Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial
What this study found
End-study 25(OH)D levels were higher with supplementation (800 IU/day: 82.5 nmol/L; 3200 IU/day: 105.4 nmol/L vs 53.6 nmol/L in controls). Breakthrough infection risk did not decrease (aHR 1.28 [0.89-1.84] for 800 IU/day; aHR 1.17 [0.81-1.70] for 3200 IU/day). IgGAM anti-Spike titres, neutralising antibody titres, and IFN-γ responses showed no inter-arm differences. Conclusion: Vitamin D replacement raises 25(OH)D but does not influence SARS-CoV-2 vaccine efficacy or immunogenicity; not recommended as an adjunct to vaccination in adults with suboptimal baseline vitamin D.
- Study & population
- Three sub-studies nested within the CORONAVIT randomized controlled trial.
- Intervention
- Vitamin D3 capsules; 800 IU/day or 3200 IU/day for 6 months; one capsule daily; mailed to participants; unsupervised usage.
- Key limitation
- Open-label design; baseline imbalance in pre-vaccination SARS-CoV-2 infection; randomisation not stratified by sub-study participation; no baseline 25(OH)D data for the no-offer arm; limited power to assess severe disease due to few hospitalizations.
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Open PDFOriginal abstract
Vitamin D deficiency has been reported to associate with the impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost the immunogenicity and efficacy of SARS-CoV-2 vaccination by conducting three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated the effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n = 2808) investigated the effects of vitamin D supplementation on the risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n = 1853) investigated the effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n = 100) investigated the effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. In total, 1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford–AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Mean follow-up 25(OH)D concentrations were significantly elevated in the 800 IU/day vs. no-offer group (82.5 vs. 53.6 nmol/L; mean difference 28.8 nmol/L, 95% CI 22.8–34.8) and in the 3200 IU/day vs. no offer group (105.4 vs. 53.6 nmol/L; mean difference 51.7 nmol/L, 45.1–58.4). Vitamin D supplementation did not influence the risk of breakthrough SARS-CoV-2 infection in vaccinated participants (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in the supernatants of S peptide-stimulated whole blood. In conclusion, vitamin D replacement at a dose of 800 or 3200 IU/day effectively elevated 25(OH)D concentrations, but it did not influence the protective efficacy or immunogenicity of SARS-CoV-2 vaccination when given to adults who had a sub-optimal vitamin D status at baseline.