Background Hesitancy and incomplete vaccination against coronavirus disease 2019 (COVID-19) remains an obstacle to achieving herd immunity. Because of fear of vaccine reactions, patients with medical and allergic co-morbidities express heightened hesitancy. Limited information is available to guide these patients. We sought to identify factors associated with mRNA-based COVID-19 vaccines hesitancy and reactogenicity. Methods We surveyed employees of a multi-site health system in central Pennsylvania who were offered the COVID-19 vaccine (N = 18, 740) inquiring about their experience with the Moderna and Pfizer-BioNTech mRNA-based vaccines. The survey was administered online using the REDCap platform. We used multivariable regression analysis to determine whether a particular factor(s) (e.g., demographics, selected co-morbid allergic and medical conditions, vaccine brand, and prior COVID-19) were associated with vaccine reactogenicity including the occurrence and severity of local and systemic reactions. We also explored factors and reasons associated with vaccine hesitancy. Results Of the 5709 who completed the survey (response rate, 30.4%), 369 (6.5%) did not receive the vaccine. Black race and allergy to other vaccines were associated with vaccine hesitancy. Reaction intensity following the first vaccine dose and allergic co-morbidities were associated with incomplete vaccination. Older individuals (>60 years) experienced less reactogenicity. Females had higher odds of local and systemic reactions and reported more severe reactions. Asians reported more severe reactions. As compared to Pfizer-BioNTech, the Moderna vaccine was associated with higher odds of vaccine reactions of higher severity. Prior COVID-19 resulted in more severe reactions following the first dose, but less severe reactions following the second dose. Conclusions Targeted campaigns to enhance vaccination acceptance should focus on Black individuals, females, and those with allergic co-morbidities. Prior COVID-19 caused more severe reactions after the first but not the second vaccine dose. Moderna vaccine caused more vaccine reactions. Lessons learned from the early rollout of COVID-19 vaccine may serve to inform future novel vaccine experiences.
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