COVID-19 Vaccine Hesitancy Worldwide: A Concise Systematic Review of Vaccine Acceptance Rates

Utility of vaccine campaigns to control coronavirus 2019 disease (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and healthcare workers appears to have a decisive role in the successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on 25 December 2020. Results from 31 peer-reviewed published studies met the inclusion criteria and formed the basis for the final COVID-19 vaccine acceptance estimates. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). However, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors and nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In the majority of survey studies among the general public stratified per country (29/47, 62%), the acceptance of COVID-19 vaccination showed a level of ≥70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East and North Africa, Sub-Saharan Africa, Eastern Europe, Central Asia, Middle and South America. Addressing the scope of COVID-19 vaccine hesitancy in various countries is recommended as an initial step for building trust in COVID-19 vaccination efforts.


Introduction
Based on the Strategic Advisory Group of Experts on Immunization (SAGE), vaccine hesitancy is the term used to describe: "delay in acceptance or refusal of vaccination despite availability of vaccination services" [1]. Factors that affect the attitude towards acceptance of vaccination include complacency, convenience and confidence [1,2]. Complacency denotes the low perception of the disease risk; hence, vaccination was deemed unnecessary. Confidence refers to the trust in vaccination safety, effectiveness, besides the competence of the healthcare systems. Convenience entails the availability, affordability and delivery of vaccines in a comfortable context [2].
The complex nature of motives behind vaccine hesitancy can be analysed using the epidemiologic triad of environmental, agent and host factors [3,4]. Environmental factors include public health policies, social factors and the messages spread by the media [5][6][7]. The

Materials and Methods
This review was conducted following the PRISMA guidelines [44]. Published papers in PubMed/Medline that aimed at evaluating COVID-19 vaccine hesitancy/vaccine acceptance using a survey/questionnaire were eligible for inclusion in this review.
Only studies in English language that met the inclusion criteria were considered in this review. The inclusion criteria were: (1) peer-reviewed published articles indexed in PubMed; (2) survey studies among the general population, health-care workers, students, or parents/guardians); (3) the major aim of the study was to evaluate COVID-19 vaccine acceptance/hesitancy; and (4) publication language was English.
Screening of titles and abstracts was conducted, followed by data extraction for the following items: date of survey, country/countries in which the survey was conducted, target population for survey (e.g., general public, healthcare workers, and students), total number of respondents, and COVID-19 vaccine acceptance rate (which included the number of respondents who answered: agree/somewhat/completely agree/leaning towards yes/definitely yes).

Results
A total of 178 records were identified, and following the screening process, a total of 30 articles were included in this review ( Figure 1). In addition, data collected in a recently published article that surveyed the general public residing in Jordan and Kuwait were added to the final analysis [45].

Materials and Methods
This review was conducted following the PRISMA guidelines [44].
Published papers in PubMed/Medline that aimed at evaluating COVID-19 vaccine hesitancy/vaccine acceptance using a survey/questionnaire were eligible for inclusion in this review.
Only studies in English language that met the inclusion criteria were considered in this review. The inclusion criteria were: (1) peer-reviewed published articles indexed in PubMed; (2) survey studies among the general population, health-care workers, students, or parents/guardians); (3) the major aim of the study was to evaluate COVID-19 vaccine acceptance/hesitancy; and (4) publication language was English.
Screening of titles and abstracts was conducted, followed by data extraction for the following items: date of survey, country/countries in which the survey was conducted, target population for survey (e.g., general public, healthcare workers, and students), total number of respondents, and COVID-19 vaccine acceptance rate (which included the number of respondents who answered: agree/somewhat/completely agree/leaning towards yes/definitely yes).

Results
A total of 178 records were identified, and following the screening process, a total of 30 articles were included in this review ( Figure 1). In addition, data collected in a recently published article that surveyed the general public residing in Jordan and Kuwait were added to the final analysis [45].

Characteristics of the Papers Included in This Review
A total of 30 published papers were analysed in this review, with an additional recently published article that focused on COVID-19 vaccine acceptance in Jordan and Kuwait to yield a total of 31 studies. These studies comprised surveys on COVID-19 vaccine

Characteristics of the Papers Included in This Review
A total of 30 published papers were analysed in this review, with an additional recently published article that focused on COVID-19 vaccine acceptance in Jordan and Kuwait to yield a total of 31 studies. These studies comprised surveys on COVID-19 vaccine acceptance from a total of 33 different countries. Surveys were done most commonly in the UK (n = 6), followed by France and the US (n = 5, for each country), and China and Italy (n = 4, for each country). Dates of survey distribution ranged from February 2020 until December 2020. A few studies were conducted in more than one country, including the study by Lazarus et al., involving 19 countries and the study by Neumann-Böhme et al., involving seven European countries [46,47].
Stratified per country, a total of 60 surveys were found with the largest sample size (n = 5114) in the study conducted in the UK by Freeman et al., while the smallest sample size (n = 123) was found in the study conducted in Malta by Gretch et al., among general practitioners and trainees [48,49]. Out of these 60 surveys, 47 were among the general public, eight surveys were among healthcare workers (doctors, nurses, or others), three surveys were among parents/guardians and two surveys involved University students ( Table 1). Surveys were most commonly conducted in June or July (23/60, 38%), followed by March or April (20/60, 33%).

Rates of COVID-19 Vaccine Acceptance
The results of the COVID-19 vaccine acceptance rates in different studies included in this review and stratified by country are shown in Table 1. Classified per study, the highest vaccine acceptance rates (>90%) among the general public were found in four studies from Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the contrary, the lowest vaccine acceptance rates (<60%) among the general public were found in seven studies to be from Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). In Figure 2, COVID-19 vaccine acceptance rates are shown per country, with the latest estimate used for countries with multiple studies. Figure 2. COVID-19 vaccine acceptance rates worldwide. For countries with more than one survey study, the vaccine acceptance rate of the latest survey was used in this graph. The estimates were also based on studies from the general population, except in the following cases where no studies from the general public were found (Australia: parents/guardians; DRC: healthcare workers; Hong Kong: healthcare workers; Malta: healthcare workers).
For the eight studies conducted on healthcare workers, three surveys reported vaccine acceptance rates below 60%, with the highest rate being among doctors in Israel (78.1%) and the lowest vaccine acceptance rate (27.7%) reported among healthcare workers in the Democratic Republic of the Congo (DRC).
For the three studies conducted among parents/guardians, the vaccine acceptance rates were more than 70%. For the two studies among University students, the vaccine acceptance rate was 57.3% in Malta (excluding university staff), and 86.1% in Italy.
Male sex was associated with significantly higher rates of COVID-19 vaccine in 15 countries/studies, while the age was a significant factor in 11 studies/countries. For the eight studies conducted on healthcare workers, three surveys reported vaccine acceptance rates below 60%, with the highest rate being among doctors in Israel (78.1%) and the lowest vaccine acceptance rate (27.7%) reported among healthcare workers in the Democratic Republic of the Congo (DRC).
For the three studies conducted among parents/guardians, the vaccine acceptance rates were more than 70%. For the two studies among University students, the vaccine acceptance rate was 57.3% in Malta (excluding university staff), and 86.1% in Italy.
Male sex was associated with significantly higher rates of COVID-19 vaccine in 15 countries/studies, while the age was a significant factor in 11 studies/countries.

Changes in COVID-19 Vaccine Acceptance over Time in Countries with Multiple Survey Studies
In countries with multiple surveys over time, the following changes in COVID-19 vaccine acceptance rates were observed. In the UK, the vaccine acceptance rate was 79.0% in April, 83.0% in May, 71.5% in June, 64.0% in July and 71.7% in September/October. In France, the vaccine acceptance rate ranged from 62.0% to 77.1% in March/April and was 58.9% in June. In Italy, the vaccine acceptance rate was 77.3% in April, 70.8% in June and it reached 53.7% in September.
For the vaccine acceptance rates in the US, it was 56.9% in April, and ranged from 67.0% to 75.0% in May, and reached 75.4% in June. In China, three studies reported high rates of vaccine acceptance with the first study that reported a vaccine acceptance rate of 91.3% in March, the second study reported a rate of 83.5% in May and the third study reported a rate of 88.6% in June.

Discussion
Vaccine hesitancy is an old phenomenon that represents a serious threat to the global health, as shown by the resurgence of some infectious diseases (e.g., outbreaks of measles and pertussis) [76][77][78][79][80]. The huge leaps in developing efficacious and safe COVID-19 vaccines within a short period were unprecedented [81][82][83]. Nevertheless, COVID-19 vaccine hesitancy can be the limiting step in the global efforts to control the current pandemic with its negative health and socio-economic effects [43,84,85].
Assessing the level of population immunity necessary to limit the pathogen spread is dependent on the basic reproductive number for that infectious disease [86]. The latest estimates on COVID-19, pointed out a range of 60-75% immune individuals that would be necessary to halt the forward transmission of the virus and community spread of the virus [87][88][89]. Vaccine cost, effectiveness and duration of protection appear as important factors to achieve such a goal [83,90,91]. However, vaccine hesitancy can be a decisive factor that would hinder the successful control of the current COVID-19 pandemic [43,92]. Thus, estimates of vaccine acceptance rates can be helpful to plan actions and intervention measures necessary to increase the awareness and assure people about the safety and benefits of vaccines, which in turn would help to control virus spread and alleviate the negative effects of this unprecedented pandemic [93,94]. Evaluation of attitudes and acceptance rates towards COVID-19 vaccines can help to initiate communication campaigns that are much needed to strengthen trust in health authorities [24].
In this review, a large variability in COVID-19 vaccine acceptance rates was found. However, certain patterns can be deduced based on descriptive analysis of the reported vaccine acceptance rates. First, in East and South East Asia, the overall acceptance rates among the general public were relatively high. This includes more than 90% acceptance rates in Indonesia, Malaysia and one study from China [51,52,59]. Another two surveys on the general public in China reported vaccine acceptance rates of more than 80%, with an additional survey in South Korea that reported a rate of 79.8% [46,63]. A later survey from Shenzhen, China, by Zhang et al., which surveyed parents/guardians who were factory workers, on their acceptability of children COVID-19 vaccination reported a lower rate of 72.5% compared to previous studies [71]. Similarly, an online survey on Australian parents showed an acceptance rate of 75.8%, dropping from a rate of 85.8% in April among adults in Australia who were surveyed in April 2020 [68,95]. The lowest COVID-19 vaccine acceptance rate among the general public in the region was reported by Lazarus et al., in Singapore (67.9%) [46]. The relatively high rates of vaccine acceptance in the region were attributed to strong trust in governments [46]. Additionally, the only survey in India reported a vaccine acceptance rate of 74.5% [46]. The relatively high rates of COVID-19 vaccine acceptance might be related to stronger confidence in vaccine safety and effectiveness, as reported previously in Asia [27].
However, two studies that dated back to the early part of the pandemic (February and March) among nurses in Hong Kong reported low rates of COVID-19 acceptance (40.0% and 63.0%) [50,55]. Likewise, Kabamba Nzaji et al. reported a very low rate of COVID-19 vaccine acceptance among healthcare workers in the DRC (27.7%) [56]. This issue is alarming considering the front-line position of healthcare workers in fighting the spread and effects of the COVID-19 pandemic, which put them at a higher risk of infection, and hence their higher need for protective measures [96][97][98].
Additionally, the vaccine acceptance rates were relatively high in Latin America, where results from Brazil and Ecuador reported more than 70% acceptance rates [46,58]. This was also seen in the survey from Mexico with a vaccine acceptance rate of 76.3% [46].
In Europe, the results were largely variable, with countries around the Mediterranean reporting vaccine acceptance rates as low as 53.7% in Italy, and 58.9% in France; no surveys among the general public in Malta were found [46,72]. The results in Italy and France can be viewed from the perspective of lacking confidence in the safety of these vaccines, since such a negative attitude was reported previously in these countries [27]. In addition, low rates of COVID-19 vaccine acceptance were reported among students and healthcare workers in Malta-44.2% and 52.0%, respectively [73,74]. Variable results were also reported in other European countries with rates as high as 80.0% in Denmark, and as low as 56.3% in Poland [46,47]. The vaccine acceptance rates were even lower in Russia (54.9%), which needs further evaluation considering the heavy toll of COVID-19 on the country [29,46]. Variability in vaccine acceptance rates was also seen in the UK, US and Canada over the course of the pandemic [61,62,64,65,70]. Additionally, a drop in COVID-19 vaccine acceptance was noticed in a few European countries, which is in line with the recent report by Lin et al. [24]. Such patterns of COVID-19 vaccine hesitancy were consistent with a previous report that showed relatively high rates of vaccine hesitancy in Western and Eastern Europe, in addition to Russia [26]. The aforementioned low rates can be linked to lower confidence in vaccine safety and effectiveness in these regions [26].
The Middle East was among the regions with the lowest COVID-19 vaccine acceptance rates globally. The acceptance rate was the lowest in Kuwait (23.6%), followed by Jordan (28.4%), Saudi Arabia (64.7%) and Turkey (66.0%) [45,62,75]. Such low rates can be related to the widespread embrace of conspiratorial beliefs in the region, with its subsequent negative attitude towards vaccination [23,[99][100][101]. However, the highest vaccine acceptance rate was reported in Israel (75.0%); however, this rate was much lower among nurses surveyed in the same study (61.1%) [53].
Only two surveys among the general public in African countries reported an acceptance rate of 81.6% in South Africa and 65.2% in Nigeria [46]. Early knowledge, attitudes and practices survey study towards COVID-19, from North-Central Nigeria, reported an acceptance rate of barely 29.0%, which highlights the need for more studies for an accurate depiction of COVID-19 vaccine hesitancy in Africa due to possible large regional and sub-regional variations [102]. Thus, more studies are recommended in Africa to address COVID-19 vaccine hesitancy in the continent. Despite the previous findings of an overall low prevalence of vaccine hesitancy in Eastern Africa, the attitude towards the newer vaccines, including those of COVID-19, remains a study topic that has not been explored to a large degree [12]. Besides Africa, more studies are needed from Central Asia, Eastern Europe, Central and South America to reach reliable conclusions about the scope of COVID-19 vaccine hesitancy around the globe.
Finally, the assessment of the role of sex and age in COVID-19 vaccine hesitancy revealed that males were more inclined to accept COVID-19 vaccines. This can be related to their higher perception of COVID-19 dangers and lower belief in conspiratorial claims surrounding the disease [45,99,101]. These variables should be considered for an accurate interpretation of COVID-19 acceptance rates, since sampling bias, particularly in sex distribution, can affect the reported rates.
The limitations of this review include the sole dependence on PubMed in the search study; however, this approach was done to provide a concise and succinct evaluation of COVID-19 vaccine hesitancy. This approach could have resulted in the inevitable missing of a few relevant studies tackling the subject of this review (e.g., the study by Head et al. assessing SARS-CoV-2 vaccination intentions among adults in the US) [103]. In addition, the research studies included in this review represented cross-sectional studies, which can be seen as snapshots of vaccine hesitancy status in each country/region, with different sampling strategies, which may partly explain the differences in vaccine acceptance rates reported in various studies from a single country. Thus, the results should be interpreted with extreme caution since they cannot predict the future changes in vaccine acceptance rates. The results of this study can be used as an initial motivation and guide for future studies and vaccine awareness campaigns. Finally, an important limitation was related to the different approaches used to express the willingness to accept COVID-19 vaccines in various studies (i.e., some studies used a binary response of yes/no, while others used a scale of strongly agree/agree/neutral/disagree/strongly disagree to deduce the inclination towards vaccine acceptance, etc.); thus, this variable should be taken into account for accurate comparisons of vaccine acceptance rates between different studies.

Conclusions
Large variability in COVID-19 vaccine acceptance rates was reported in different countries and regions of the world. A sizable number of studies reported COVID-19 acceptance rates below 60%, which would pose a serious problem for efforts to control the current COVID-19 pandemic. Low COVID-19 vaccine acceptance rates were more pronounced in the Middle East, Eastern Europe and Russia. High acceptance rates in East and South East Asia would help to achieve proper control of the pandemic. More studies are recommended to assess the attitude of general public and healthcare workers in Africa, Central Asia and the Middle East besides Central and South America. Such studies would help to evaluate COVID-19 vaccine hesitancy and its potential consequences in these regions, and around the globe.
The major challenges that could face successful implementation of COVID-19 vaccination programs to fight the unprecedented pandemic include mass manufacturing of vaccines, its fair distribution across the world and the uncertainty regarding its long-term efficacy. However, vaccine hesitancy can be the major hindrance of the control efforts to lessen the negative consequences of COVID-19 pandemic, at least in certain countries/regions.
The widespread prevalence of COVID-19 vaccine hesitancy mandates collaborative efforts of governments, health policy makers, and media sources, including social media companies. It is recommended to build COVID-19 vaccination trust among the general public, via the spread of timely and clear messages through trusted channels advocating the safety and efficacy of currently available COVID-19 vaccines.
Funding: This research received no external funding.
Institutional Review Board Statement: Ethical approval is not applicable for this systematic review since data from previous published studies in which informed consent was obtained by primary investigators was analyzed.

Informed Consent Statement: Not applicable.
Data Availability Statement: Data supporting this systematic review are available in the reference section. In addition, the analyzed data that were used during the current systematic review are available from the author on reasonable request. Acknowledgments: I wish to express my sincere gratitude for the reviewers, for their insightful and valuable comments on the manuscript that helped to improve its quality to a great degree.

Conflicts of Interest:
The author declares no conflict of interest.