Abstract

Background/Objectives: Although the protective effects of zinc against COVID-19 are documented, its impact on COVID-19 vaccine immunogenicity remains unknown. Methods: We conducted a prospective study involving a cohort of 79 Japanese individuals (aged 21–56 years; comprising three subcohorts) and measured their serum zinc levels pre-vaccination and anti-SARS-CoV-2 IgM/IgG levels pre- and post-vaccination over 4 months. Results: Serum zinc concentrations ranged between 74–140 and 64–113 ug/dL in male and female individuals, respectively, with one male and 11 female participants exhibiting subclinical zinc deficiency (60–80 ug/dL). Mixed models for antibody titers, accounting for the subcohorts, repeat measurements, and covariates (e.g., vaccine type, sex, age, height, steroid use, medical history, smoking and drinking habits, perceived stress, and sleep disturbances) showed positive effects of zinc on IgM (p = 0.012) and IgG (p = 0.013) in 45 female individuals with 255 observations. However, a similar association was not found in the 34 male participants with 162 observations. This discrepancy may be attributed to one participant being included in the subcohort with frequent repeat measurements (10 repeats in 4 months). COVID-19 mRNA vaccine immunogenicity was enhanced in the participants with high baseline blood zinc levels within the reference range. Conclusions: Our findings underscore the relevance of maintaining adequate zinc levels before vaccination, which can be achieved through a balanced diet and healthy lifestyle choices.