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.
Keywords: BNT162b2 Pfizer; ChAdOx1 nCoV-19 Oxford–AstraZeneca; antibody; breakthrough SARS-CoV-2 infection; interferon gamma; randomised controlled trial; vitamin D.
【저자키워드】 randomised controlled trial, antibody, Breakthrough SARS-CoV-2 infection, vitamin D., interferon gamma, ChAdOx1 nCoV-19 Oxford–AstraZeneca, BNT162b2 Pfizer, 【초록키워드】 SARS-CoV-2, IgG, IgM, Efficacy, vaccination, Vitamin D, SARS-COV-2 infection, 25-hydroxyvitamin D, interferon, risk, SARS-CoV-2 vaccine, BNT162b2, Pfizer, dried blood spot, Whole blood, IgA, neutralising antibody, response, Acute respiratory infection, Vitamin, Follow-up, ChAdOx1 nCoV-19, SARS-CoV-2 vaccination, boost, IFN-γ, Protective, cellular response, Vitamin D status, Concentration, dose, deficiency, Vitamin D supplementation, 95% CI, adjusted hazard ratio, titres, blood sample, participant, mean difference, titre, circulating, supernatant, offer, neutralising antibody titre, Effect, concentrations, venous, collected, significantly, reported, investigated, elevated, determine, baseline, of BNT162b2, randomised controlled, vitamin D supplement, 【제목키워드】 SARS-CoV-2, Vitamin D, Controlled, influence,