Immunization-related stress and stress-related responses of mucosal versus intramuscular COVID-19 vaccination among adults in China

Background: In late 2022, China became the first country to roll out mucosal COVID-19 vaccines. No prior study has yet compared the immunization stress-related responses (ISRR) among different routes of COVID-19 vaccine delivery. We aimed to compare the immunization-related psychological stress and ISRR between mucosal and intramuscular COVID-19 vaccines. Methods: A cross-sectional questionnaire survey using a biopsychosocial framework design was performed from January 11 to 20, 2023. Adults with COVID-19 vaccination were eligible for the study, and a total of 1073 adults participated with community-based sample. Primary outcomes were the psychological stress levels and prevalence of ISRR. Multivariate regression models were employed to compare these outcomes between the two vaccination groups. The potential mediating effects of stress on vaccination and ISRR were examined using bootstrap sampling method. To further ensure the robustness of our results, sensitivity analysis with propensity score matching was performed. Findings: In the univariate analysis, participants who received mucosal vaccination reported significantly lower stress levels compared to those who received intramuscular vaccination (3.39 +/- 3.02 vs. 3.93 +/- 3.24, P = .006). The prevalence of overall ISRR was significantly lower in the mucosal group compared to the intramuscular group (38.4% vs. 47.9%, P = .002). Multivariate regression models revealed that participants who received mucosal vaccination had a significantly lower stress level (beta = -0.516, 95% CI: -0.852 to -0.180; P = .003) and 38.7% fewer overall ISRR (OR = 0.613, 95% CI: 0.427 to 0.881; P = .008), particularly in terms of neurological symptoms. The immunization-related stress mediated the association between vaccination type and ISRR, with indirect effects estimated at 0.0663 (95% CI: 0.0195 to 0.1346) for overall ISRR. Conclusions: Mucosal COVID-19 vaccination was associated with reduced psychological stress and physical responses, as compared to intramuscular vaccination, which may contribute to increased trust and compliance with routine or mass vaccination efforts in the future.