From Trust to Skepticism: Longitudinal Qualitative Insights on Uncertainties in COVID-19 Vaccine Messaging Among Trial-Engaged Participants Across the United States

Mass vaccination emerged as a key public health strategy during the COVID-19 pandemic. Yet, greater attention is needed to understand the shifting dynamics of vaccine messaging amid rampant uncertainty across the United States, including its impact on vaccine uptake behaviors over time. Our study presented a unique opportunity to longitudinally explore how perceived uncertainties in COVID-19 vaccine messaging shaped vaccine uptake behaviors among participants enrolled in a remote, nationwide COVID-19 trial in the United States. In-depth, semi-structured qualitative interviews were conducted virtually across two timepoints (T1: December 2020 to March 2021, <i>n</i> = 19; T2: January to February 2022, <i>n</i> = 11). Analysis was guided by immersion crystallization; an inductive and deductive approach to identifying themes and the relationships between them. Most participants (aged 32-74) resided in California (T1: 58%, T2: 45%) and self-identified as white (T1: 63%; T2: 73%) and/or cisgender women (T1: 63%; T2: 55%). All participants expressed interest in the COVID-19 vaccine at T1, among which 21% received their first dose as members of priority groups. By T2, all participants obtained the primary COVID-19 vaccine series, and 73% received a booster. Key themes included: (1) self-efficacy in the absence of cohesive information; (2) shifting guidelines heightened perceived barriers and uncertainties; and (3) unresolved messaging fueled skepticism and reduced trust in public health. Findings underscore how logistical and scientific uncertainties can be detrimental to long-term vaccine uptake, albeit acting in different ways. Communicating uncertainties necessitates iterative, public participation to advance health and scientific literacy, mitigate vaccine skepticism, and sustain vaccine uptake behaviors over time.