COVID-19 vaccination has resulted in decreased hospitalization and mortality, particularly among those who have received a booster. As new effective pharmaceutical treatments are now available and requirements for non-pharmaceutical interventions (e.g. masking) are relaxed, perceptions of the risk and health consequences of SARS-CoV-2 infection have decreased, risking potential resurgence. This June 2022 cross-sectional comparative study of representative samples in New York City (NYC, n = 2500) and the United States (US, n = 1000) aimed to assess differences in reported vaccine acceptance as well as attitudes toward vaccination mandates and new COVID-19 information and treatments. NYC respondents reported higher COVID-19 vaccine acceptance and support for vaccine mandate than U.S. respondents, yet lower acceptance for the booster dose. Nearly one-third of both NYC and U.S. respondents reported paying less attention to COVID-19 vaccine information than a year earlier, suggesting health communicators may need innovation and creativity to reach those with waning attention to COVID-19-related information.