Keywords
COVID-19; vaccination; refusal; acceptance; risk factors.
This article is included in the Sociology of Health gateway.
This article is included in the Emerging Diseases and Outbreaks gateway.
This article is included in the Sociology of Vaccines collection.
COVID-19; vaccination; refusal; acceptance; risk factors.
At the beginning of 2021, the coronavirus disease 2019 (COVID-19) vaccination program involving several designs including protein subunit, vector, inactivated, and mRNA, was started.1 Currently, referring to data presented on Our World in Data, this vaccination program has included 84.6% of the global population, and the reason the rest of the population (15.4%) did not receive vaccination is still unknown.2 The high number of vaccinated country populations is the result of the hard work of various parties, and this may be associated with factors such as the seriousness of governments in promoting vaccination programs, equitable distributions of vaccines, hard work of healthcare workers, good public awareness about the importance of vaccination, and good promotion of vaccines to populations who have the power to hesitate about vaccines.3 Contrarily, in the unvaccinated population, several factors may contribute to hesitation, including fear of harmful ingredients in vaccines, distrust of pharmaceutical companies, lack of knowledge about COVID-19, belief that a healthy lifestyle and a good diet are enough to fight against COVID-19, preference for natural immunity, lack of seriousness from the government in promoting vaccination programs, religious rules suggesting not to vaccinate, and limited information regarding the safety of vaccination. These factors have been reported to trigger hesitancy and refusal of the COVID-19 vaccination.4–7 In our previous study, we had explored the global prevalence of COVID-19 vaccination hesitancy and its potential associated factors.8 However, because the hesitancy population consists of hesitancy and refusal populations, and the refusal population can influence people in their circle to become hesitant or refuse the COVID-19 vaccine, the prevalence of the COVID-19 vaccine refusal should also be investigated.
It is widely known that new vaccines or vaccine candidates are commonly hesitated against or rejected by the public. Before the COVID-19 pandemic, this phenomenon has been widely reported in several cases, such as: dengue,9 malaria,10 Ebola,11 chikungunya,12 and monkeypox.13 This might be caused by poor public knowledge regarding the vaccine, including the poor knowledge of vaccine efficacy and side effects. In the case of COVID-19, this phenomenon might be affected by multiple factors, and theoretically, the factors had been contextualized into three major categories, including poor knowledge of vaccination programs, socioeconomic status, and social interaction.14 Moreover, recently, influencers in their podcasts discussed the rejection of the COVID-19 vaccine, which is a dilemma that can govern people in society to reject COVID-19 vaccinations, thereby threatening the success of the COVID-19 vaccination program.15 However, to date, there are no precise data on the prevalence of COVID-19 vaccination refusal and its potential associated factors. Several previous studies have investigated the refusal of COVID-19 vaccines; however, the results of these studies have been inconclusive. In the present study, we seek to explore the global prevalence of COVID-19 vaccination refusal and identify the associated factors using a meta-analysis approach.
A meta-analysis following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol was carried out from August to November 2022 (PROSPERO: CRD42022384562). The PRISMA checklist in our study is provided in Figshare.16 A systematic search was implemented in PubMed, Scopus, and Web of Science; and the information was collected from each relevant article to determine the prevalence and associated factors of COVID-19 vaccines refusal.
Pre-defined eligibility criteria were assigned prior to performing the search strategy. The inclusion criteria were: (1) assessment of the prevalence of COVID-19 vaccination refusal, and (2) investigation of the factors associated with COVID-19 vaccination refusal. Articles with double publications, letters to the editor, commentaries, and reviews were excluded.
PubMed, Scopus, and Web of Science were searched up to November 5th, 2022. Before conducting a search for the primary outcome, we identified the factors that might have an impact on the incidence of refusal of COVID-19 vaccines. The potential keywords adapted from medical subject headings were applied: “vaccine,” “vaccination,” or “immunization;” “COVID-19” or “coronavirus disease 2019;” “refusal” or “rejection” or “acceptance.” The search strategy used only English words. In case of duplication, articles with a lower sample size used in the study were excluded. Moreover, to acquire additional references, a search on the reference list of related articles was also carried out. A pilot form was used to collect data from each study and consisted of the following items: (1) first author name, (2) time of publication, (3) design of study, (4) study period, (5) Newcastle–Ottawa scale (NOS), (6) the event rate of COVID-19 vaccination refusal, and (7) factors associated with COVID-19 vaccination refusal. Data were collected by FT, JKF, APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, and YSP.
The NOS was used to assess the quality of potential articles. We included articles of moderate and high quality, and low quality articles were excluded. A score of 0–3, 4–6, and 7–9 indicated low, moderate, and high quality articles, respectively. The NOS assessment was performed by JKF, APK, and EAP using the NOS pilot form. Disagreements were resolved through discussion.
The primary endpoints of our study were the global prevalence and factors associated with COVID-19 vaccination refusal. The potential factors associated with the refusal of COVID-19 vaccination were: age group, gender, marital status, educational attainment, employment status, healthcare-related job, socioeconomic status (SES), urbanity, presence of children and elderly people at home, individual with medical background, history of testing for COVID-19, family member/friend ever diagnosed with COVID-19, personal history of COVID-19 diagnosis, history of hospitalization due to COVID-19 among people in a social circle, and history of previous vaccination.
Data are presented as n (%). The statistical analysis consisted of the following parameters: publication bias among studies, heterogeneity among studies, event rate, and odds ratio with a 95% confidence interval (OR95%CI). Publication bias was assessed using Egger’s test. A p-value of less than 0.05 indicated that publication bias existed among studies. The heterogeneity in our study was determined using the Q test. Evidence of heterogeneity was found if the p-value was less than 0.10. If we found heterogeneity among studies, we applied the random effects model, and in cases where no heterogeneity was found, we used a fixed effects model. The cumulative event rate of COVID-19 vaccine refusal was calculated using a single-arm meta-analysis with a dichotomous model, and the pooled OR95%CIs of factors associated with the refusal of COVID-19 vaccination were calculated using the Mantel-Haenszel method. The analysis was performed using the R package (RStudio version 4.1.1, R Studio, California, MA, USA).
A total of 3,422 papers and 4 papers were assessed from the databases and reference lists of related articles, respectively. In the initial evaluation, we excluded 33 papers because of duplication, and 3,318 papers because of irrelevant topics. Subsequently, 75 articles were included in further review. We further excluded 17 articles as they were reviews and 34 articles because of insufficient data. Finally, the data retrieved from 24 articles were analyzed to estimate the cumulative prevalence and factors associated with COVID-19 vaccination refusal.17–40 The flow diagram of article selection in our study is outlined in Figure 1, and the characteristics of the articles included in our study are listed in Table 1.
Our analysis identified that the cumulative prevalence of the refusal to COVID-19 vaccination was 12% (event rate: 0.12; 95%CI: 0.10, 0.15; p Egger: 0.5290; p Heterogeneity<0.0001; p<0.0001) (Figure 2A). Subsequently, sub – group analysis found that the prevalence of the refusal to COVID-19 in general population was 20% (Figure 2B), healthcare workers 10% (Figure 2C), and students 11% (Figure 2D).
Table 2 and Figures 3–5 summarize the factors associated with refusal of COVID-19 vaccination. Our calculation revealed that six of the 15 factors had a significant impact on COVID-19 vaccine refusal. We found that an increased risk of COVID-19 vaccine refusal was observed in the following covariates: female (Figure 3A), educational attainment lower than an undergraduate degree (Figure 4A) and living in rural areas (Figure 5B).
In contrast, the decreased risk of refusal of COVID-19 vaccination was affected by the following factors: high socioeconomic status (Figure 5A), history of previous vaccination (Figure 3B), and individuals with medical background (Figure 4B).
Our analysis using the Q test revealed that two variables (single marital status and history of testing for COVID-19) had no evidence of heterogeneity; thereafter, we applied a fixed-effects model. In contrast, a random-effects model was applied to the other covariates (Table 2). Subsequently, our analysis using Egger’s test revealed that the marital status and ever tested for COVID-19 covariates had a risk of publication bias (Table 2).
Our meta-analysis revealed that the prevalence of refusal to undergo the COVID-19 vaccination was 12%. Our findings were lower than those reported by Cenat et al. and Robinson et al.41,42 In our study, we had a larger sample size than those reported by in these studies. Moreover, studies by Cenat et al. and Robinson et al. also involved articles that reported COVID-19 vaccination hesitancy.41,42 It is well known that the terminologies of refusal and hesitancy to vaccinate are different, and not everyone is hesitant to vaccinate. Thus, it can be assumed that the context of previous studies has a gap in the definition of vaccine refusal. Therefore, our study may provide better data on the prevalence rate of COVID-19 vaccination refusal. Moreover, we also reported the prevalence of COVID-19 vaccination refusal in some subgroup populations: general population, healthcare workers, and students. We found that healthcare workers had the lowest prevalence of COVID-19 vaccination refusal, followed by students, and the general population. Our current findings indicate that vaccination knowledge might affect our findings. We assumed that healthcare workers and students may have a better knowledge of vaccination programs than the general population. This assumption is supported by the results of previous studies, which found that healthcare workers and students had better knowledge of COVID-19 vaccination than the general population,43,44 and this factor was also shown to contribute to the acceptance of vaccination programs.45
Our study found that the increased risk of COVID-19 vaccination refusal was higher in females and individuals with educational levels below an undergraduate degree (BSc). In contrast, lower risk of COVID-19 vaccination refusal was found in individuals with a history of previous vaccination and medical background. Our current findings suggest that the factors related to knowledge of COVID-19 vaccination had the potential to affect the refusal to vaccinate against COVID-19. As previously reported, a study revealed that females lacked literacy regarding COVID-19 vaccination than males.46 This may be due to the fact that the majority of females are housewives, and therefore, may have less social interaction than males, as they are based at home rather than going out to work.47 This possibility might contribute to the lack of knowledge on COVID-19 vaccination in the female population. Furthermore, one study found that the majority of the side effects of COVID-19 vaccination were found among female individuals48 Taken together, those factors may affect the decision to accept or refuse the vaccines. Moreover, individuals with educational level below the undergraduate (BSc) degree might have an inadequate source of literature regarding COVID-19 vaccination compared to those with an educational level higher than an undergraduate (BSc) degree. In the context of vaccination knowledge, a study found that educational attainment was one of the predictors of vaccination knowledge, where lower educational attainment was associated with poorer knowledge of vaccination.49 Therefore, the population with an educational level below the undergraduate (BSc) degree might have insufficient consideration for COVID-19 vaccination compared to those with an educational level higher than the undergraduate (BSc) degree. Further, individuals with a history of previous vaccination and a medical background may have adequate information regarding the importance of COVID-19 vaccination, therefore, may have sufficient awareness regarding COVID-19 vaccination. Previous studies found that individuals with a medical background had better knowledge of COVID-19 vaccination than the general population.43,44 Likewise, a study revealed that individuals with a history of previous annual vaccination had good awareness and knowledge of the importance of vaccination programs.50 Prior to the COVID-19 pandemic, studies have widely reported that knowledge on disease prevention and the good practice of health behavior had a significant impact on the acceptance rate of vaccination in the case of Monkeypox, Ebola, and Dengue.51–53 Thus, this might imply that this population (individuals with a history of previous vaccination and medical background) has a low rate of refusal to vaccinate against COVID-19, as reported in our meta-analysis.
Our study also found that a higher risk of COVID-19 vaccination refusal was observed in rural than urban populations, and a lower risk of COVID-19 vaccination refusal was observed in individuals with high SES than in those with low SES. Currently, the precise explanations regarding the reasons underlying our findings might be difficult to explain and might have differences between each region. However, we can propose the following reasons: social privileges, administrative requirements, and social circles. First, in the social privilege aspect, individuals with high SES might have certain pride if they have been vaccinated, while this pride might not belong to the rural population. Studies found that COVID-19 vaccination was considered a socioeconomic privilege and political ideology,54 while the rural population did not consider that the COVID-19 vaccine was a privilege and tended to have poor perception toward vaccine safety.55 The second reason is administrative requirements. Individuals with high SES might need COVID-19 vaccination as an administrative requirement for their activities; for example, business, travelling, and carrier requirements as the World Health Organization (WHO) has implemented a COVID-19 vaccine certificate as an administrative requirement for travel or business.56 However, these administrative requirements were not necessary for rural individuals, as the majority of rural individual jobs are in private and traditional sectors, such as farmers, fishermen, and manual laborers.57,58 The third factor is social circle. Individuals with high SES might have social circles that interact with high intellectual content, whereas in rural populations, their social circle might be limited to their neighbors with similar intellectual contents. This factor might also indirectly contribute to the understanding of COVID-19 vaccinations, and consequently, affect their decision to accept or refuse the COVID-19 vaccine. This is supported by previous studies that revealed that SES was associated with the level of knowledge of vaccination programs and physical health status.59,60 Moreover, our previous study on dengue also revealed that SES was one of the predictive indicators for the acceptance of vaccination.53
Our meta-analysis is one of the first to report the prevalence of COVID-19 vaccination refusal and the potential factors associated with refusal of COVID-19 vaccination. Our study also had a larger sample size compared to previous meta-analyses in a similar context.41,42 The findings of our study might serve as the initial step to prevent the failure of COVID-19 vaccination programs. By identifying the potential factors associated with refusal to vaccinate against COVID-19, we expect that governments may provide advanced intervention to those populations. As previously reported, the main concern to obtain public trust regarding the COVID-19 vaccines was the lack of adequate evidence from long-term and large-scale studies on the effectiveness and safety of COVID-19 vaccination.61 However, several studies have provided suggestions on how to provide interventions to the refusal population: providing reliable information regarding the COVID-19 pandemic and the COVID-19 vaccination, providing customized, effective, ethical, and evidence-based communication; and the information should be provided by community leaders and healthcare practitioners.62–64
Our meta-analysis has several limitations. First, several potential confounding factors, such as the level of knowledge about COVID-19 vaccination, attitude toward COVID-19 prevention, government regulation, types of vaccine, environmental factors, and the source of literature regarding COVID-19 vaccination, were not included in the analysis due to the lack of available data. Second, the sample size in our present study was limited; therefore, further studies involving larger sample sizes are needed. Third, our meta-analysis could not reflect the prevalence of the global numbers because the proportion of sample sizes in each region was unequal. Fourth, all articles included in our analysis were cross-sectional studies. Further meta-analyses involving only randomized controlled trials are required.
In conclusion, we revealed that the cumulative prevalence of the refusal to COVID-19 vaccination was 12%, the highest in the general population, and the lowest in the healthcare worker subgroup. The individuals with the following characteristics are found increased risk to refuse COVID-19 vaccination: female, having an educational attainment lower than an undergraduate degree, and living in a rural area, while the following factors are associated with reduced risk to refuse COVID-19 vaccination: high socioeconomic status, history of previous vaccination, and individuals with a medical background.
Conceptualization: FT, JKF, GS; Data Curation: FT, JKF, GS, APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP; Formal Analysis: JKF, APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP; Investigation: FT, JKF, GS, LW, APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP; Project Administration: APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP; Resources: APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP; Methodology: FT, JKF, GS, LW, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP; Software: FT, JKF, APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP; Visualization: APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP, CC, KD, HH; Supervision: FT, JKF, GS, LW, CC, KD, HH; Validation: FT, JKF, LW, CC, KD, HH; Writing – Original Draft Preparation: FT, JKF, LW, APK, EAP, RPP, MR, TA, MN, SW, GP, AP, QA, MVPHM, RY, YSP; Writing – Review & Editing: FT, JKF, GS, LW, CC, KD, HH. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript.
All data underlying the results are available as part of the article and no additional sources of data are required.
Figshare: PRISMA checklist for ‘The refusal of COVID-19 vaccination and its associated factors: A meta-analysis’. https://doi.org/10.6084/m9.figshare.21617979.v1. 16
Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).
We thank Lembaga Pengelola Dana Pendidikan (LPDP) and Kementerian Pendidikan, Kebudayaan, Riset, dan Teknologi (Kemendikbudristek) Republic of Indonesia for supporting this project.
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Are the rationale for, and objectives of, the Systematic Review clearly stated?
Yes
Are sufficient details of the methods and analysis provided to allow replication by others?
No
Is the statistical analysis and its interpretation appropriate?
Yes
Are the conclusions drawn adequately supported by the results presented in the review?
Yes
References
1. Gori D, Capodici A, La Fauci G, Montalti M, et al.: COVID-19 Vaccine Refusal and Delay among Adults in Italy: Evidence from the OBVIOUS Project, a National Survey in Italy.Vaccines (Basel). 2023; 11 (4). PubMed Abstract | Publisher Full TextCompeting Interests: No competing interests were disclosed.
Reviewer Expertise: Epidemiology
Are the rationale for, and objectives of, the Systematic Review clearly stated?
Partly
Are sufficient details of the methods and analysis provided to allow replication by others?
Partly
Is the statistical analysis and its interpretation appropriate?
Yes
Are the conclusions drawn adequately supported by the results presented in the review?
Partly
References
1. Larson H, Jarrett C, Eckersberger E, Smith D, et al.: Understanding vaccine hesitancy around vaccines and vaccination from a global perspective: A systematic review of published literature, 2007–2012. Vaccine. 2014; 32 (19): 2150-2159 Publisher Full TextCompeting Interests: Currently have funding to study vaccine hesitancy for dengue vaccines in Peru, where our research touched on hesitancy for COVID-19 vaccination as well.
Reviewer Expertise: Dengue epidemiology; arbovirus epidemiology; systematic review
Alongside their report, reviewers assign a status to the article:
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Version 1 13 Jan 23 |
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