Influence of vitamin D supplementation on SARS-CoV-2 vaccine efficacy and immunogenicity (preprint)

ABSTRACT

Background and Aims: Vitamin D deficiency has been reported to associate with impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost immunogenicity and efficacy of SARS-CoV-2 vaccination. Methods: We conducted three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated effects of offering vitamin D supplements at a dose of 800 or 3200 IU per day vs. no offer on risk of acute respiratory infections, including COVID-19, in UK adults with circulating 25-hydroxyvitamin D concentrations under 75 nmol/L. Sub-study 1 (n=2808) investigated effects of vitamin D supplementation on risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n=1853) investigated 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 effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. Results: 1945/2823 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Vitamin D supplementation did not influence risk of breakthrough SARS-CoV-2 infection (800 IU per day vs. no offer adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU per day vs. no offer 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or interferon-gamma concentrations in supernatants of S peptide-stimulated whole blood. Conclusions: Among adults with sub-optimal baseline vitamin D status, vitamin D replacement at a dose of 800 or 3200 IU per day did not influence protective efficacy or immunogenicity of SARS-CoV-2 vaccination. Clinical Trial Registration ClinicalTrials.gov NCT04579640.