ABSTRACT
Vaccination of adults is central to control of SARS-CoV-2/COVID-19 and multiple other infectious diseases.
Failure to engage in vaccine uptake is a complex, multilevel systems problem--individual factors such as
fatalism, lack of factual information, medical and government mistrust, and political affiliation are all known
inhibitors to vaccine uptake, as are community factors such as lack of access, limited delivery mechanisms,
and messages from untrusted communicators. Thus, addressing vaccine hesitancy requires a multilevel
intervention that aligns and addresses individual, relational, and structural elements to incorporate all of the
necessary and sufficient components to increase uptake. COVID-19 vaccine uptake among Appalachian
residents has been unacceptably low, with rates plateauing months ago. Appalachian Kentucky encompasses
a number of population characteristics that add up to a "perfect storm" for a vaccine hesitant population.
Structurally, the region is rural, with many communities geographically isolated and lacking access to health
care. This, in addition to poverty, low education and high levels of chronic disease, place this population at
significant risk of complications and mortality due to COVID-19 infection. In a population that historically has
distrusted institutions, vaccination interventions must leverage culturally appropriate community partnerships
and strategies. The purpose of this community-engaged study is to optimize SARS-CoV-2 vaccine uptake by
this highly vulnerable Appalachian Kentucky population. We will achieve three specific aims: Aim 1: Using a
community-engaged approach, elucidate: a) key themes for message content and framing that address
individual-level factors, b) trusted communicators to deliver culturally-sensitive messages, and c) structural
barriers to effective vaccine delivery, as well determining to what degree such factors are community-specific
versus more generalizable. Aim 2: Using a cluster randomized trial design, assess the efficacy of a multilevel
intervention that delivers individual-level target messaging tailored for theme and presentation by trusted local
communicators AND that provides structural components to facilitate easy and acceptable access to
vaccination delivery. Aim 3: Determine the process factors that affect reach, acceptance, and implementation
fidelity for the intervention components, as well as necessary adaptation components for broader
transferability, dissemination, and delivery of the intervention. Our long-term goal as a research team is to
develop effective, multilevel intervention strategies that can be used to address vaccine hesitancy in
Appalachian and similar rural populations for existing vaccination concerns.