Abstract
Background Despite ongoing waves of Coronavirus disease 2019 (COVID-19) infections, including significant surges such as the 10th wave, understanding the impact of messenger RNA (mRNA) COVID-19 vaccination on infection risk and associated behavioral changes remains crucial. This study aims to urgently evaluate the effects of mRNA COVID-19 vaccination on COVID-19 infection rates and related behaviors among participants of the Yamato Project, which includes employees of Japanese small and medium-sized enterprises (SMEs). Methods A case-control study was conducted using data collected from a survey administered by the Japan Small and Medium Enterprise Management Council in December 2023. Participants included individuals who were part of the Yamato Project, not necessarily limited to SME employees. The survey gathered information on demographic characteristics, COVID-19 infection status, vaccination history, health status before January 2020, and various preventive behaviors. The primary outcome was the presence or absence of COVID-19 infection. Data were analyzed using univariate and multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between vaccination status and COVID-19 infection. Results A total of 913 participants were included in the final analysis. The adjusted ORs for COVID-19 infection among vaccinated individuals compared to unvaccinated individuals were 1.85 (95% CI: 1.33-2.57, p < 0.001). The odds of contracting COVID-19 increased with the number of vaccine doses: one to two doses (OR: 1.63, 95% CI: 1.08-2.46, p = 0.020), three to four doses (OR: 2.04, 95% CI: 1.35-3.08, p = 0.001), and five to seven doses (OR: 2.21, 95% CI: 1.07-4.56, p = 0.033). Behavioral analysis indicated that a reduced frequency of bathing and exercising was significantly associated with higher COVID-19 infection rates (p < 0.05). Conclusions The study observed a higher reported incidence of COVID-19 infection among vaccinated individuals during the pandemic period, which increased with the number of vaccine doses received. This paradoxical finding may be influenced by various factors, including immune response mechanisms, such as antibody-dependent enhancement (ADE) or original antigenic sin, behavioral changes, and exposure risk. Understanding these factors is crucial for urgently enhancing public health strategies and vaccination programs.