Testing Theory-Enhanced Messaging to Promote COVID-19 Vaccination Among Adults: Randomized Controlled Trial (Preprint)

BACKGROUND Uptake of the COVID-19 vaccine has been low in the United States despite ongoing public health recommendations. This has been linked to many factors, including pandemic fatigue; reduced risk perception; dis- and misinformation; and, more recently, symptoms of depression and anxiety. Novel communication and messaging strategies are one potential approach to promote vaccine uptake. OBJECTIVE This randomized controlled trial aimed to fill research gaps by testing the effect of 2 communication-based approaches―the use of a short attitudinal inoculation message and cognitive behavioral therapy (CBT) kernel messaging―compared to standard public health messaging on vaccine uptake in a cohort of adult US residents. METHODS We completed a 3-arm, parallel-group, assessor-blinded stratified randomized trial between April 15, 2024, and May 2, 2024. Individuals were eligible if they were aged ≥18 years and (1) had received at least one dose of the COVID-19 vaccine but (2) had not received COVID-19 vaccine doses since September 11, 2023, and (3) had not been infected with SARS-CoV-2 in the previous 3 months. We purposively sampled eligible individuals with and without symptoms of anxiety and depression. Participants were randomly allocated to the (1) attitudinal inoculation intervention, (2) CBT kernel intervention, or (3) standard public health messaging intervention. RESULTS By the 4-week follow-up, COVID-19 vaccination uptake was low overall (17/1403, 1.2%, 95% CI 0.6%-1.8%) and did not significantly differ by study arm―1.5% (7/469) in the CBT kernel arm (95% CI 0.4%-2.8%), 0.9% (4/466) in the inoculation arm (95% CI 0%-1.8%), and 1.3% (6/468) in the standard arm (95% CI 0.3%-2.4%). Compared to the standard arm, the CBT kernel intervention yielded a risk difference (RD) of 0.3% (95% CI −1.3% to 1.8%) and a risk ratio (RR) of 1.21 (95% CI 0.41-3.59); the inoculation intervention yielded an RD of −0.4% (95% CI −1.8% to 1%) and an RR of 0.69 (95% CI 0.19-2.44). Reported SARS-CoV-2 infections and vaccine uptake did not differ by anxiety or depression symptoms. At baseline, approximately one-third of participants (466/1403, 33.21%) reported high willingness to receive another COVID-19 vaccine dose, with no significant differences across arms. At the 4-week follow-up, willingness remained similar across groups (CBT kernel vs standard arm: RD=−0.3%, 95% CI −6.3% to 5.8%, and RR=0.99, 95% CI 0.79-1.25; inoculation vs standard arm: RD=7%, 95% CI 0.8%-13.3%, and RR=1.23, 95% CI 0.98-1.53). Willingness did not differ by mental health status. CONCLUSIONS Successful efforts to increase uptake of the COVID-19 vaccine via theory-enhanced messaging remain elusive. Findings underscore the challenges of shifting behavior through messaging alone in a context of declining public trust and a diminished sense of urgency years after the onset of the COVID-19 pandemic. Ongoing research is needed to better understand and address informational and behavioral barriers to vaccination. CLINICALTRIAL ClinicalTrials.gov NCT06119854; https://clinicaltrials.gov/study/NCT06119854