COVID-19 vaccine hesitancy among the vaccinated: a cross-sectional survey

Introduction

As of October 3, 2023, more than 67.66 million cases of coronavirus disease 2019 (COVID-19) have been confirmed globally, with 6.88 million deaths reported across 192 countries and territories (1). Non-drug interventions, such as large-scale physical distancing measures, appear to slow the spread of this infectious disease; however, there is no evidence that these measures will completely halt the rising number of COVID-19 infections (2). Thus, it is crucial that vaccines are administered to reduce morbidity and mortality, and to prevent COVID-19 complications (3).

The purpose of a vaccine is to achieve herd immunity by vaccinating a sufficient portion of the population, thereby preventing the further transmission of pathogens between individuals (2). Since the identification of the COVID-19 virus and its genome, the scientific community has worked tirelessly on more than 300 vaccine projects. Approximately 40 vaccines are currently in clinical trials, three of which have completed phase III clinical trials with positive results (4). Despite the successful development of effective COVID-19 vaccines, herd immunity is unlikely to be achieved due to vaccine hesitancy and low vaccine acceptance (5).

Vaccine hesitancy is defined as delaying receiving or refusing vaccination despite the proven effectiveness of vaccines. In 2019, the World Health Organization (WHO) listed vaccine hesitancy as one of the top 10 global health threats (6). Vaccine hesitancy leads to a reduced willingness to vaccinate and is a significant barrier in preventing infectious diseases and reducing vaccination rates (7). Despite adequate efforts by the government to promote the COVID-19 vaccine, vaccine hesitancy prevails due to misinformation (8) and anti-vaccine rhetoric (9). The Chinese government has highlighted the positive features of the vaccines, especially their safety and efficacy. However, the decision to receive a vaccine ultimately lies with the public, which comprises groups prone to vaccine hesitancy due to concerns related to their comorbidities (10), and doubts about the reliability of vaccines, and the correct interval between dosing (11). Given the large population and complex social demographics of China, it is crucial to explore the factors affecting vaccine hesitancy to ensure the successful implementation of the vaccine (12).

In many countries, a series of reports has focused too closely on the serious side effects of vaccines, especially those used in national immunization programs, significantly and negatively increasing vaccine hesitancy (13-15). Misinformation about vaccination side effects have created significant barriers to achieving broad vaccine coverage and herd immunity. To address these barriers, governments, public health officials, and organizations have prepared evidence-based information to raise public awareness of vaccinations to achieve broad vaccine coverage for COVID-19 (14).

A number of studies have examined individuals’ willingness and hesitancy to receive the first dose of the COVID-19 vaccine (5,16-23). Wang et al. examined COVID-19 vaccination status and the factors influencing the decision of the elderly to refuse or contemplate refusing the vaccine in a nationally representative sample of 12,900 participants in China (16). Kim et al. investigated unvaccinated and vaccinated individuals and found that misinformation may play a key role in the vaccination behavior of unvaccinated people (17). However, a study has explored the willingness and hesitancy of individuals to receive a second dose and ongoing doses of the COVID-19 vaccine after the first dose, despite strong evidence that the second dose and ongoing doses of the COVID-19 vaccine reduce the number of cases with severe infections, prevent hospitalizations, and lower morbidity and mortality (11). As Guangdong Province is the most populous province in China, a representative population from this province was chosen for the study sample.

This study aimed to investigate vaccine hesitancy by exploring and identifying the enablers and barriers to receiving the second dose of the COVID-19 vaccine in a small cohort who had already received the first dose of the COVID-19 vaccine. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-666/rc).

Methods

A cross-sectional survey was administered to 959 individuals who were scheduled to receive a second injection of the inactivated COVID-19 vaccine at Guangdong Provincial People’s Hospital from February 18 to February 23, 2021. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Guangdong Provincial People’s Hospital (No. KY-Q-2021-185-01), and written informed consent was obtained from all participants.

Participants were included in the study if they met the following inclusion criteria: (I) were aged 18 to 59 years; (II) provided informed consent to receive the COVID-19 vaccine; and (III) received the second dose of the COVID-19 vaccine 4 weeks after the first dose of the COVID-19 vaccine. Participants were excluded from the study if they met any of the following exclusion criteria: (I) were allergic to any ingredients contained in the COVID-19 vaccine, including the additives and substances used in its preparation; (II) had acute diseases, severe chronic diseases, or suffered from acute attacks of chronic diseases and fever; (III) had a history or family history of convulsions, epilepsy, Guillain-Barre syndrome, other progressive neurological diseases, encephalopathy, or psychosis; (IV) had previously experienced a severe allergic reaction to vaccines, including acute allergic reactions, urticaria, eczema, dyspnea, angioneurotic edema, or abdominal pain, or any neurological reactions; (V) were pregnant; and/or (VI) had previously experienced a severe allergic reaction after the first dose of the COVID-19 vaccine.

The inactivated COVID-19 vaccine (Sinovac vaccine) was used in this study. The first injection was administered intramuscularly in the left deltoid muscle. After 28 days, the second injection was administered intramuscularly in the right upper arm deltoid.

The survey was independently developed based on comprehensive literature searches (24,25). It comprises three parts: part 1 examines the socio-demographic characteristics of the surveyed participants; part 2 investigates the motivational factors and enablers of the COVID-19 vaccine; part 3 investigates vaccine hesitancy and the barriers to COVID-19 vaccination. The degree of willingness to vaccinate against COVID-19 was measured on a scale with scores ranging from 0 (lowest) to 5 (highest).

As no clinical study had been conducted on vaccine hesitancy in relation to the first dose of the COVID-19 vaccine at the time of our investigation, we conducted a pre-experiment and found a vaccine hesitancy rate of 30%. With an α of 0.05 and a confidence interval width of 0.1, a minimum sample size of 896 was calculated. To ensure an adequate representation, a total sample size of 959 participants was set.

Statistical analysis

SPSS 25.0 was used for the data analysis in this study. The data are presented as the number (n) with the percentage (%), or the mean with the standard deviation. The descriptive analysis was performed using the t-test for the continuous variables, and the Chi-squared test or Fisher’s exact test for the categorical variables. Factors identified as statistically significant (P<0.1) in the univariate analysis were included in the multivariate logistic regression model. All the statistical tests were two-sided, and a P<0.05 was considered statistically significant.

Results

Socio-demographic characteristics of the surveyed participants

The mean age of the 959 participants was 43.23±9.86 years, 80.0% were male, 84.8% were married, 34.9% had additional commercial insurance, and 11.5% had a history of allergies. Hypertension accounted for 8.7% of all comorbidities.

Of the participants, 90% indicated that their “doctors’ advice on the vaccine alleviated their fear”. Further, 82.2% of the participants indicated they were “worried about the possibility of infecting family members with COVID-19”, and 81.3% indicated that having “many vaccinated colleagues and friends” informed their decision to receive the COVID-19 vaccine (Table 1).

Of the participants who were classified as being hesitant to receive the COVID-19 vaccine, 43.8% indicated that they were “not aware of the effectiveness of the COVID-19 vaccine”, 41.7% indicated that they were concerned “about the safety and side effects of the COVID-19 vaccine”, and 41.0% indicated that they “lacked an understanding of the data on COVID-19 vaccination-related adverse events”.

Comparison of socio-demographic characteristics, potential enabling factors, and potential barriers between the weak and strong vaccination willingness groups

The participants were grouped according to their willingness to receive the COVID-19 vaccine. Participants with scores of 5 were allocated to the strong vaccination willingness group, while those with scores of 0–4 were allocated to the weak vaccination willingness group. Of the participants, 716 (74.7%) were allocated to the weak vaccination willingness group (Table 1).

The participants in the weak vaccination willingness group had a mean age of 41.14±9.96 years, while those in the strong vaccination willingness group had a mean age of 43.94±9.73 years. As detailed in Table 2, statistically significant differences were observed between the two groups in terms of age (P<0.001) and gender (P<0.001). Notably, the weak vaccination willingness group comprised 174 men (71.6%), and the strong vaccination willingness group comprised 593 men (82.8%). Further, the weak vaccination willingness group comprised 192 (79.0%) married individuals, and the strong vaccination willingness group comprised 621 (86.7%) married individuals. A statistically significant difference was observed between the two groups in terms of marriage status (P=0.004; Table 2). In the weak vaccination willingness group, 30.0% of the participants had purchased additional commercial insurance, compared to 36.6% in the strong vaccination willingness group (P=0.06; Table 2). There were no statistically significant differences between the two groups in terms of their education level, allergy history, and comorbidities such as hypertension, diabetes, hyperuricemia, hyperlipidemia, and asthma.

Comparison of potential enabling factors between the weak and strong vaccination willingness groups

A comparison of the two groups revealed that having “many vaccinated colleagues and friends” increased participants’ willingness to receive the COVID-19 vaccine (82.8% vs. 77.0%, P=0.043; Table 2). There were no statistically significant differences between the two groups in terms of their responses to the questions related to their “high-risk occupational exposure to COVID-19”, concern about “infecting family members with COVID-19”, and “doctors’ advice on vaccination” alleviating their fear (P>0.05).

Comparison of potential barriers between the weak and strong vaccination willingness groups

A comparison of the two groups revealed that a lack of knowledge about the efficacy of the COVID-19 vaccine (39.8% vs. 55.6%, P<0.001), a misunderstanding of the safety and side effects of the vaccine (32.8% vs. 67.9%, P<0.001), counseling difficulties after receiving the COVID-19 vaccine (15.8% vs. 31.7%, P<0.001), and the misinterpretation of data on adverse events related to the COVID-19 vaccine (34.6% vs. 59.7%, P<0.001) were barriers to ongoing COVID-19 vaccination (Table 2). Conversely, there were no statistically significant differences between the two groups in terms of their previous adverse reactions to vaccinations, fear of vaccination needles, distrust of medical institutions, or the high cost of the COVID-19 vaccine (P>0.05).

Multivariate logistic regression analysis of the factors affecting regular and ongoing COVID-19 vaccines

The variables with P<0.10 in the univariate analysis (Table 2) were included in the multivariate logistic regression model. Notably, males [odds ratio (OR) =0.58; P=0.005], older individuals (OR =0.97; P=0.001), those with additional commercial insurance (OR =0.65; P=0.02), those who were married (OR =0.57; P=0.007), and those who had many vaccinated colleagues and friends (OR =0.58; P=0.007) were more willing and less hesitant to receive the COVID-19 vaccines (Table 3). However, the participants who misunderstood the safety and side effects of the COVID-19 vaccine (OR =4.34; P<0.001), and misinterpreted the data on adverse events related to the COVID-19 vaccine (OR =1.59; P=0.03) were more likely to hesitate having regular and ongoing COVID-19 vaccines (Table 3).

Discussion

In our study, all the participants had received their first COVID-19 vaccine, and most (74.7%) had a strong willingness to vaccinate against COVID-19. A recent survey of 13,426 people from 19 countries revealed that 71.5% received a COVID-19 vaccine before the WHO-certified vaccine was used (18), which was similar to the percentage reported in our study. In our study, 80.0% (n=767) of the participants were male, and 84.8% (n=813) were married. The multivariate logistic regression analysis revealed that sex, age, and marriage status affected the COVID-19 vaccine acceptance rate. The participants who were single and female were more likely to show COVID-19 vaccine hesitancy. Similarly, acceptance rates for influenza vaccines are lower in pregnant women (24). Qin et al. investigated the attitudes of individuals of reproductive age to COVID-19 vaccination during pregnancy (25). The effects of the COVID-19 vaccine on pregnancy are now clearer, but further research needs to be conducted to alleviate concerns about the effects of the COVID-19 vaccine on pregnancy, and thus increase the willingness of such individuals to receive the COVID-19 vaccine and reduce vaccine hesitancy.

In relation to the factors informing vaccination decision-making, 90% of the participants indicated that their “doctors’ advice on vaccination alleviated their fear”, which highlights the importance of doctors discussing the efficacy and safety of vaccines; however, the doctors’ advice still had minimal effects on participants’ willingness to vaccinate. Having “many vaccinated colleagues and friends” was the second most highly rated factor affecting participants’ willingness to receive the COVID-19 vaccine. Thus, mass vaccination clinics may increase vaccination acceptance and reduce vaccine hesitancy, leading to improved herd immunity.

Many of the participants indicated that they would prefer to receive vaccinations with routine immunization schedules prior to an anticipated epidemic or outbreak rather than an emergency vaccination or mandatory vaccination. Notably, mandatory vaccination in certain countries has been shown to increase vaccine hesitancy (26). A survey on COVID-19 vaccine acceptance suggested that mandatory vaccination increases vaccine hesitancy; thus, promoting voluntary vaccination may represent a better approach (18).

Marketing campaigns directed at public education on the COVID-19 vaccine have been shown to address the issue of vaccine hesitancy (27). Marketing principles can be used to influence the behaviors of target audiences, benefiting individuals and society (27). The Australian Government successfully developed the Australian Immunization Program, a marketing strategy that included a variety of initiatives and social marketing approaches to raise awareness of the importance of vaccination. This program increased the childhood vaccination rate to 91% (28). Further, a social marketing campaign for human papillomavirus vaccination in the USA was launched to raise parental awareness and reduce barriers to vaccination in major rural areas among girls aged 11–12 years, and resulted in a significant increase in the uptake of the vaccination among girls aged 9–13 years (29).

Misunderstandings of the safety and side effects of the vaccine, and a lack of understanding of the data on the adverse events associated with the COVID-19 vaccine, are barriers to COVID-19 vaccination and are factors affecting vaccine hesitancy. The issue of safety appears to be more important than that of effectiveness. Several studies on the COVID-19 vaccine have shown that the main factors influencing vaccine hesitancy include concerns about vaccine safety and side effects (19-21). Kreps et al. conducted a study of 1,971 American adults and found that the lower the incidence of major adverse reactions, the higher the likelihood of vaccination (22). This survey suggests that data on the effectiveness, safety, and adverse events related to various COVID-19 vaccines should be published in a timely manner, and media platforms enabling public access to such data should also be provided.

Another potential barrier may be related to the costs of the vaccine. In this survey, 3.2% of the participants indicated that they believed that the costs of “COVID-19 vaccines are important”. Thus, the implementation of free COVID-19 vaccine programs may reduce the economic costs for individuals in China. We also examined the effect of purchasing additional commercial insurance, and found that this directly affected participants’ willingness to receive the COVID-19 vaccine, such that those with commercial insurance coverage were more likely to receive the COVID-19 vaccine and showed the least vaccine hesitancy. Thus, we found that the cost of the COVID-19 vaccine did not represent the participants’ greatest concern, and the long-term absence of post-vaccination adverse events may help reduce vaccine hesitancy.

Another study in the USA confirmed that commercial insurance is a determining factor in reducing vaccine hesitancy and in increasing acceptance of the COVID-19 vaccine (30). Seale et al. conducted a survey of the COVID-19 vaccine in Australia, and found that patients with commercial insurance had a lower rate of vaccine hesitancy and a higher rate of acceptance for the COVID-19 vaccine (31). The provision of private commercial insurance for the second dose of the COVID-19 vaccine may increase people’s willingness to receive the COVID-19 vaccine and reduce vaccine hesitancy.

A survey of the influenza vaccine acceptance rate by health care workers in the public health sector revealed that fear of needles was a predictor of vaccine hesitancy or vaccine rejection (P≤0.042) (32). A study of the influenza vaccine acceptance rate in 1,039 participants from 14 universities revealed that a fear of needles was the main reason for vaccine hesitancy or even rejection (33).

Our study had several limitations. First, under China’s COVID-19 vaccination policy, individuals must be aged 18 to 60 years to receive the vaccine, which differs to the age ranges detailed in other countries’ COVID-19 vaccination policies. Second, all our study participants had received the first dose of the COVID-19 vaccine, which may indicate lower levels of vaccination hesitancy. As a result, our findings on willingness to vaccinate may be biased and may not be fully representative of populations who have never received a COVID-19 vaccine. Third, our study results may not be fully generalizable to real-world settings, and the self-reported responses could have introduced information bias.

To address these limitations and to reduce vaccine hesitancy for the second dose and ongoing booster doses, an education program on COVID-19 vaccines needs to the established, outlining the efficacy and safety issues, and providing questions and answers. Based on our study, we developed an education table for COVID-19 vaccines answering common questions raised by the public (Table 4). Further, the use of booster doses as part of ongoing COVID-19 vaccination programs requires further research. Recent research suggests that participants who received a booster had lower mortality due to COVID-19 than participants who did not receive a booster (34). A longer interval between the second dose and the booster doses was associated with small improvements in vaccine effectiveness (34). Similar findings have also been observed in individuals with a history of prior infection (i.e., a longer interval between infection and vaccination was found to be associated with increased protection) (35).

Conclusions

This study showed that there was a high level of acceptance of COVID-19 vaccination among the adult population in China during the pandemic. The participants who were male, married, had many vaccinated colleagues and friends, and had additional commercial insurance were more willing and less hesitant to receive the COVID-19 vaccine. Conversely, those who misunderstood the safety and side effects of the vaccine and misinterpreted adverse event data showed higher vaccine hesitancy and a lower level of vaccine acceptance. Our study facilitated the development of COVID-19 vaccination education material, which seeks to alleviate the public’s concerns about the safety and efficacy of the vaccine and potential adverse events related to the vaccine. Ultimately, our findings may increase people’s willingness to vaccinate and reduce vaccine hesitancy. The successful delivery of the COVID-19 vaccine could reduce morbidity, mortality, and hospitalization, including intensive care unit (ICU) and critical care admission, which in turn could decrease the social and economic burden. This study paves the way for future research on the feasibility of an ongoing COVID-19 vaccination program in China with a particular focus on doses administered after the second dose and booster doses, which have been internationally shown to protect against serious COVID-19 infection.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-666/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-666/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-666/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-666/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committees of Guangdong Provincial People’s Hospital (No. KY-Q-2021-185-01) and written informed consent was obtained from all participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: L. Huleatt)