Combined copper and zinc deficiency is associated with reduced SARS-CoV-2 immunization response to BNT162b2 vaccination

Figures

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  Fig. 1. Study design, serum copper and ceruloplasmin concentrations and longitudinal dynamics. A The schematic diagram of the study design is shown. B Serum copper and ceruloplasmin concentrations show a positive linear correlation. C There are no apparent differences in serum copper concentrations during the study period. D Similarly, serum ceruloplasmin concentrations are relatively constant during the observation period. The correlation analysis was performed using Spearman's rank correlation; results are indicated as inset.

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  Fig. 2. Dynamic changes in SARS-CoV-2 IgG concentrations according to baseline copper and ceruloplasmin status. A Comparison of SARS-CoV-2 IgG titers in probands at baseline and week 3, 6, and 24 post vaccination with different copper status (Q1<1024.55 μg/L; Q2 1024.55–1211 μg/L; Q3 >1211 μg/L) at baseline indicates significant differences at 3 weeks post vaccination. B The comparison of SARS-CoV-2 IgG titers in relation to baseline Ceruloplasmin status (Q1<340.70 mg/L; Q2 340.70–453.23 mg/L; Q3 >453.23 mg/L) does not reveal significant differences. Two-sided Kruskal-Wallis test was used to assess differences.

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  Fig. 3. Correlation of baseline copper and ceruloplasmin with vaccination parameters. A Baseline copper concentration shows a linear correlation with SARS-CoV-2 IgG levels at baseline and week 3 post vaccination. B Baseline ceruloplasmin and SARS-CoV-2 IgG levels were not associated at week 3 post vaccination. C Correlation analysis of the inhibitory activity with baseline copper concentration at week 3 post vaccination indicates a moderate interaction. D No correlation between inhibition activity and baseline ceruloplasmin concentration at week 3 post vaccination was noted. Data were analyzed by Spearman's rank correlation.

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  Fig. 4. SARS-CoV-2 IgG according to double Q1 (deficiency) of copper and zinc at baseline. A Comparison of SARS-CoV-2 IgG titers in probands of different baseline copper and zinc status (Double Q1: copper <1024.55; zinc <764.3) indicates significant differences at 3 and 6 weeks post vaccination. B Comparison of neutralizing activity of different baseline copper and zinc status (Double Q1: copper <1024.55; zinc <764.3) baseline indicates no significant differences. Pairwise comparisons were conducted by applying the Wilcoxon-Rank-Sum test.