While considerable evidence supports the safety and efficacy of COVID-19 vaccines, a sizable population expresses vaccine hesitancy. As per the World Health Organization, vaccine hesitancy is one of the top 10 hazards to global health. Vaccine hesitancy varies across countries, with India reporting the least vaccine hesitancy. Vaccine hesitancy was higher toward COVID-19 booster doses than previous shots. Therefore, identifying factors determining COVID-19 vaccine booster hesitance (VBH) is the sine qua non of a successful vaccination campaign. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 standards. A total of 982 articles were pooled from Scopus, PubMed and Embase, while 42 articles that addressed the factors of COVID-19 VBH were finally included for further analysis. We identified factors responsible for VBH and divided them into three major groups: sociodemographic, financial, and psychological. Hence, 17 articles stated age to be a major factor for vaccine hesitancy, with most reports suggesting a negative correlation between age and fear of poor vaccination outcomes. Nine studies found females expressing greater vaccine hesitancy than males. Trust deficit in science (n = 14), concerns about safety and efficacy (n = 12), lower levels of fear regarding infection (n = 11), and worry about side effects (n = 8) were also reasons for vaccine hesitancy. Blacks, Democrats, and pregnant women showed high vaccine hesitancy. Few studies have stated income, obesity, social media, and the population living with vulnerable members as factors influencing vaccine hesitancy. A study in India showed that 44.1% of vaccine hesitancy towards booster doses could be attributed dominantly to low income, rural origin, previously unvaccinated status, or living with vulnerable individuals. However, two other Indian studies reported a lack of availability of vaccination slots, a lack of trust in the government, and concerns regarding safety as factors for vaccine hesitancy toward booster doses. Many studies have confirmed the multifactorial nature of VBH, which necessitates multifaceted, individually tailored interventions that address all potentially modifiable factors. This systematic review chiefly recommends strategizing the campaign for booster doses by identifying and evaluating the reasons for vaccine hesitancy, followed by appropriate communication (at both individual and community levels) about the benefits of booster doses and the risk of losing immunity without them.
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