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By the end of 2021, approximately 15% of U.S. adults remained unvaccinated against COVID-19, and vaccination initiation rates had stagnated. We used unsupervised machine learning (K-means clustering) to identify clusters of unvaccinated respondents based on Behavioral and Social Drivers (BeSD) of COVID-19 vaccination and compared these clusters to vaccinated participants to better understand social/behavioral factors of non-vaccination. The National Immunization Survey Adult COVID Module collects data on U.S. adults from September 26–December 31,2021 (n = 187,756). Among all participants, 51.6% were male, with a mean age of 61 years, and the majority were non-Hispanic White (62.2%), followed by Hispanic (17.2%), Black (11.9%), and others (8.7%). K-means clustering procedure was used to classify unvaccinated participants into three clusters based on 9 survey BeSD items, including items assessing COVID-19 risk perception, social norms, vaccine confidence, and practical issues. Among unvaccinated adults (N = 23,397), 3 clusters were identified: the "Reachable" (23%), "Less reachable" (27%), and the "Least reachable" (50%). The least reachable cluster reported the lowest concern about COVID-19, mask-wearing behavior, perceived vaccine confidence, and were more likely to be male, non-Hispanic White, with no health conditions, from rural counties, have previously had COVID-19, and have not received a COVID-19 vaccine recommendation from a healthcare provider. This study identified, described, and compared the characteristics of the three unvaccinated subgroups. Public health practitioners, healthcare providers and community leaders can use these characteristics to better tailor messaging for each sub-population. Our findings may also help inform decisionmakers exploring possible policy interventions. • We analyzed data from the National Immunization Survey-Adult COVID Module, September–December 2021 (n = 187,756). • Three unvaccinated subgroups were identified by K-means clustering based on social/behavioral drivers of COVID-19 vaccination. • We identified a more reachable unvaccinated subgroup that might be receptive to information promoting vaccination. • COVID-19 vaccination strategies can be tailored based on the characteristics and needs of the targeted sub-populations. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines are safe, effective, and widely available, but many adults in the U.S. have not been vaccinated for COVID-19. This study examined the associations between behavioral and social drivers of vaccination with COVID-19 vaccine uptake in the U.S. adults and their prevalence by region. A nationally representative sample of U.S. adults participated in a cross-sectional telephone survey in August–November 2021; the analysis was conducted in January 2022. Survey questions assessed self-reported COVID-19 vaccine initiation, demographics, and behavioral and social drivers of vaccination. Among the 255,763 respondents, 76% received their first dose of COVID-19 vaccine. Vaccine uptake was higher among respondents aged ≥75 years (94%), females (78%), and Asian non-Hispanic people (94%). The drivers of vaccination most strongly associated with uptake included higher anticipated regret from nonvaccination, risk perception, and confidence in vaccine safety and importance, followed by work- or school-related vaccination requirements, social norms, and provider recommendation (all p <0.05). The direction of association with uptake varied by reported level of difficulty in accessing vaccines. The prevalence of all of these behavioral and social drivers of vaccination was highest in the Northeast region and lowest in the Midwest and South. This nationally representative survey found that COVID-19 vaccine uptake was most strongly associated with greater anticipated regret, risk perception, and confidence in vaccine safety and importance, followed by vaccination requirements and social norms. Interventions that leverage these social and behavioral drivers of vaccination have the potential to increase COVID-19 vaccine uptake and could be considered for other vaccine introductions. [ABSTRACT FROM AUTHOR]