In a recent study published in the journal Vaccine, researchers investigated why more than 80% of eligible Americans have not taken their severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccine booster dose. They conducted an online survey of 2,298 respondents to evaluate the reasons underlying the low observed response.

Their results elucidate that, despite consistent research and clinical reports depicting positive, anti-coronavirus disease of 2019 (COVID-19) outcomes for individuals receiving the booster, misinformation regarding prior SARS-CoV-2 infection and vaccination, and concerns pertaining to vaccine side effects and the presence and degree of protection conferred by the booster stalled booster reception in the United States (US). These results highlight the need for additional media outreach elucidating the benefits of COVID-19 vaccines as the best intervention against the disease, especially severe infections by SARS-CoV-2.

Study: Understanding low COVID-19 booster uptake among US adults. Image Credit: angellodeco / Shutterstock

A background on COVID-19 and vaccination drives

The ongoing coronavirus disease of 2019 (COVID-19) pandemic remains one of the worst in recorded history, with the World Health Organization (WHO) COVID-19 dashboard reporting almost 771 million confirmed cases and almost 7 million deaths worldwide. Caused by the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) virus, COVID-19 has represented one of the most intensive efforts in vaccine and medication development efforts ever, with vaccination drives being second only to self-isolation in the itineraries of most governments globally.

Scientific and medical research has unanimously advocated for vaccination as the best intervention to effectively decrease COVID-19 disease severity and reduce hospitalizations, thereby attenuating mortality risk associated with the disease. COVID-19 vaccines have additionally been proven to lower the odds of COVID-19 patients developing post-acute sequelae of COVID-19 (PASC). PASC, also called ‘long COVID’ is a condition characterized by the persistence of COVID-19 symptoms months or even years following the infection, severely hampering a patient’s quality of life (QoL).

Unfortunately, unlike some vaccines which provide life-long protection against the associated disease (e.g., measles and hepatitis B), research has found that memory T and B cells associated with antibody production against COVID-19 rapidly deteriorate, resulting in loss of vaccination efficacy in as short as 120 days following initial vaccination. This demerit is compounded by the rapid rate at which SARS-CoV-2 mutates, resulting in numerous strains with reduced vaccine efficacy or outright vaccine immunity. These factors necessitate follow-up COVID-19 vaccinations with ‘boosters’ updated to account for novel and emerging COVID-19 strains, including Omicron.

To address this need, Pfizer and Moderna developed updated mRNA vaccines designed to perform against both ancestral and Omicron SAR-CoV-2 strains, which the US Food and Drug Administration (FDA) approved for emergency authorization use (EUA) and the Centres for Disease Control and Prevention (CDCP) subsequently recommended for public consumption. Unfortunately, despite public awareness drives on the benefits of booster vaccines, this intervention uptake was stalled in the US, with less than 20% of the eligible population taking a booster dose.

In order to equip clinicians, policymakers, and the general public with the knowledge required to more effectively curb COVID-19, this study investigates the reasons underlying the surprisingly low acceptance rates in the US.

About the study

This study enrolled Americans participating in the Arizona COVID-19 Cohort (CoVHORT). This study group is longitudinal in methodology and is aimed at investigating the long-term and acute effects of SAR-CoV-2 infection on Arizonans. CoVHORT participants included both individuals who had suffered from prior COVID-19 infections and those who had not. This study comprised a subset of 4827 participants selected to best represent the American populace. Participants were recruited via online survey participation requests between February 13 and March 29, 2023.

Data collection involved recording demographic- and COVID-19-associated details, especially pre-existing health conditions, severity and symptoms of SARS-CoV-2 infection, COVID-19 test results, and health behaviors. The REDCap was used for survey design and administration. As and when required, additional COVID-19-specific research questionnaires were emailed to the relevant survey respondents. Surveys are administered at study enrollment and every subsequent three months, with data collection still ongoing.

“The survey asked the question: Have you received the updated (bivalent, omicron) mRNA booster from Pfizer or Moderna? If a “no” response was recorded, participants were asked to select from a list of responses for not having received the booster; participants could choose as many responses as were applicable.”

Three themes were identified a priori, which classified responses into three associated groups – 1. Bivalent vaccine knowledge, 2. Unclear about the risks/benefits of vaccination/boosters, 3. Logistic concerns. Finally, statistical analyses focused on individuals who had received at least the initial vaccination dose, excluding respondents who had never consumed a vaccine against COVID-19. Multivariable logistic regression (MLR) analysis was used to identify trends between themes and demographic information (age, gender, education, race/ethnicity, and income). MLR models were adjusted for all the listed demographic characteristics.

Study findings

Of the 4,827 individuals contacted, 2,298 (47.6%) completed all survey rounds, 2,196 of whom had received at least one vaccination dose and were hence included in statistical analyses. Participants who completed the survey were on average, older (mean = 52.8) than those who did not (mean = 47.6), with all other demographic characteristics remaining statistically equal. This study represented a deviation from previous American vaccination reports, with 1,637 (74.5%) respondents receiving the second bivalent vaccination booster dose compared to less than 20% of the general US populace.

Results revealed that individuals who received the booster vaccine were slightly younger (mean = 50.5) than those who did not (mean = 52.8). Women (73.3%) and respondents of Hispanic ethnicity (12.6%) were less likely to take the booster dose than the overall study cohort (70.0% and 9.7%, respectively). Education and income were found to significantly impact vaccine booster reception, with individuals at lower tiers of both quintiles of both characteristics less likely to receive the booster.

Of the 559 respondents who did not receive the booster, 39.5% claimed that prior COVID-19 infection and the perceived resistance conferred by the infection was the reason for their aversion to the booster.

“The frequency of the remaining responses, in order of most-to-least reported, were as follows: I’m worried about side effects (31.5%); I don’t think this booster will add more protection over the vaccines I’ve already had (28.6%); I’m worried about the safety of the booster (23.4%); I don’t think the booster will protect me from infection (23.1%); I don’t think the booster will protect me from severe disease or death (12.2%); I didn’t know I was eligible to receive it (11.8%); I didn’t know it was available (10.0%); I don’t have time to get it (9.7%); I don’t know where to get it (7.5%); I didn’t realize it was a new booster when I saw it advertised (6.6%); I’m worried about taking time off of work to get the booster (6.1%); and I’m worried about being able to pay for the booster (1.4%).”

Conclusions

In the present study, researchers investigated the underlying reason for most (>80%) of Americans refusing booster vaccines against COVID-19 using a cohort of 2196 individuals from Arizona as representatives. The analysis revealed that misinformation about infection-conferred resistance (39.5%), and concerns about side effects (31.5%) of the vaccine were the most cited reasons for vaccine booster aversion. Concerns regarding booster safety (23.4%) and efficacy concerns (anti-COVID-19 effects [23.1%] and severe disease/death resistance [12.2%]) were the next most cited underpinnings for low vaccine acceptance.

Knowledge about the disease and vaccination effects were the least cited yet significant results of the survey. However, education and income were found to play important roles in anti-COVID-19 vaccination as a whole and not just bivalent booster dose acceptance.

Based on these results, efforts to reach out to the media and disseminate information would likely have the greatest impact on future vaccination drives, both for COVID-19 and disease outbreaks.

“In summary, the results of this work provide support for continued efforts to promote SARS-CoV-2 vaccinations and boosters among the United States population. Uptake of boosters continues to be well below the coverage needed for optimal protection of all people. The development of vaccines against SARS-CoV-2 occurred at an unprecedented speed, but implementation remains among the biggest current public health challenges as updated boosters continue to be developed and made available to the public.”