key: cord-0258704-oc67xxql
authors: Toro-Ascuy, D.; Cifuentes-Munoz, N.; Avaria, A.; Pereira-Montecinos, C.; Cruzat, G.; Zorondo-Rodriguez, F.; Fuenzalida, L. F.
title: Underlying factors that influence the acceptance of COVID-19 vaccine in a country with a high vaccination rate
date: 2021-11-01
journal: nan
DOI: 10.1101/2021.10.31.21265676
sha: b65b05e84439c611ce45f7f48b1a50c7b80e2e8f
doc_id: 258704
cord_uid: oc67xxql

Control of the COVID-19 pandemic largely depends on the effectiveness of the vaccination. Several factors including vaccine hesitancy can affect the vaccination process. Understanding the factors that underlie the willingness to accept vaccination brings pivotal information to control the pandemic. We analyzed the association between the willingness level to accept the COVID-19 vaccine, and vaccine determinants amidst the Chilean vaccination process. Individual-level survey data was collected from nationally representative samples of 744 respondents, and multivariate regression models used to estimate the association between outcome and explanatory variables. Trust in the COVID-19 vaccine, scientists, and medical professionals were found to increase the willingness to: accept the vaccine, a booster dose, annual vaccination, and children vaccination. Our results are critical to understanding the acceptance of COVID-19 vaccines in the context of a country with one of the highest vaccination rates in the world. We provide information for decision-making, policy design and communication of vaccination programs.

The sudden entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the human population in 2019 has had catastrophic consequences, with global deaths over 4.8 million worldwide 1 The success of vaccination strongly depends on underlying social factors, mainly willing to accept the vaccination, trust in stakeholders related to vaccination, vaccine-specific factors, communication and media, historical influences, religion, gender, socioeconomic, politics, geographic barriers, experience with vaccination, risk perception, and design of the vaccination program 6 . Some studies explored COVID-19 vaccine acceptance and their determinants using surveys in different countries including the United States 7-9 , United Kingdom 9-11 , China 12,13 , Indonesia 14 , Italy 15 , Ireland 10 and Japan 16 . In addition, surveys have explored vaccine acceptance in groups of European countries 17 , Arab countries 18, 19 and other countries worldwide 20 . Several of these studies have concluded that the willingness to accept the vaccine differs depending on the age, educational and economic level, credibility in government decisions and perception of risk of COVID-19 disease 7, 12, 18, [20] [21] [22] . In a global vaccine study carried out in 19 countries, it was reported that responses have had high heterogeneity depending on the country surveyed 20 ; therefore, it is important to understand the acceptance of a vaccine in each country or region 22 . Vaccination against SARS-CoV-2 remains a big challenge for most of the countries, especially those with poor economies.

Countries with broad vaccination coverage can offer key lessons on how to address the challenges about COVID-19 vaccination. In this context, the Chilean COVID-19 vaccination campaign has emerged as one of the most successful and rapid worldwide 23 . By July 2021, Chile was among the first countries in the world with more doses administered per 100 people (our world in data). However, as observed in Chile and many other countries, vaccination has slowed down after reaching over 70% of the population fully immunized.

Understanding the determinants of vaccine acceptance is key for decision-making, for establishing differentiated strategies according to the characteristics and social determinations of the population, and for identifying the subjectivities that underlie the decision-making of the people to vaccinate. Faced with the need to obtain scientific evidence amidst the Chilean vaccination campaign, we analyzed the association between the level of willingness to accept the COVID-19 vaccine and determinants of the vaccine in Chile. We focused on trust in vaccines and stakeholders and perceptions of people about effectiveness of prevention . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.

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The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint practices, infection risk, and side effects, to estimate their associations with willingness to accept the SARS-CoV-2 vaccine, booster dose, annual vaccination, and vaccination of children. Our study identified several key aspects such as a high trust in scientists and health area workers, as well as a moderate trust in the media. Our results permit projecting subjective dimensions related to the decision of the population to be vaccinated, identifying the risks and trusts of the Chilean population associated with this process, which offer keystone evidence for other countries to face the pandemic. We identified several aspects such as perception of risk and prevention practice, and trust related with the vaccination process, scientists and medical professionals, and sociodemographic variables associated with the acceptance of vaccination, booster doses, or children vaccination. The information provided by our study is relevant to improve public health communication strategies.

Between May 21 and June 21 of 2021, a total of 744 adults were recruited in Chile via online surveys. The self-application questionnaire was disseminated through social networks. A summary of the socio-demographic characteristics of respondents included in this study is shown in Table S1 . The questions were aimed at estimating four outcome variables related to willing to accept: (i) SARS-CoV-2 vaccination (0=not, 1=maybe, 2=yes), (ii) vaccine booster dose (1=yes), (iii) annual vaccination (1=totally disagree to 4=totally agree), and (iv) vaccination of children (1=totally disagree to 4=totally agree). The questionnaire also captured a set of social determinants and attributes associated with the vaccine as explanatory variables. The questions for explanatory variables were aimed at describing the perception of risk, trust, and their responses also were recorded at a level of agreement or disagreement, is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint about COVID-19 vaccines was estimated using a scale: "No trust", "Little trust", "Pretty trust", "High trust". The full questionnaire is shown in the Supplementary Information (Table   S2 ). In addition, Table S2 indicates milestones that occurred during the data collection period, according to the development of the pandemic and vaccination in Chile.

Most of the respondents (93.4% n= 695) had received at least one dose of SARS-CoV-2 vaccine at the time of the survey, whereas 3.9% (n=29) still had not decided if they would accept a SARS-CoV-2 vaccine and 2.7% (n=20) of respondents said they would definitely not accept a SARS-CoV-2 vaccine. 88.2% (n=656) of the respondents reported that they would accept an hypothetical booster dose and 57.8% (n=430) said they would definitively accept to get vaccinated every year if necessary, similar to the vaccine schedule of influenza virus. When asked if in case of having children under 16 years old, they would accept that their children could be vaccinated against SARS-CoV-2, 62.5% (n=175) reported that they would "definitively accept" a SARS-CoV-2 vaccine for their children.

Multivariate regression models were used to estimate the association between outcome and explanatory variables. Ordered logistic regression model was adjusted when analyzing the outcome variables of willingness to accept the SARS-CoV-2 vaccination, annual vaccination, and vaccination of children, while logistic regression model was used to analyze the willingness to accept the vaccine booster dose. For each outcome variable, we selected the model with best goodness of fit and parsimony using Akaike information criterion (AIC) (Table S3) .

We computed the odds ratio for selected models, which represents the ratio of the odds that an outcome variable will occur given an explanatory variable compared to the odds of the outcome occurring in the absence of the explanatory variable. If the odd ratio is greater than 1, then the explanatory variable induces a higher level of acceptance, relative to the control of other variables used in the model. Rather, an odd ratio smaller than 1 suggests that an is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint explanatory variable influences a lower willingness. We described only those results where the 95% confidence intervals exclude zero, which were deemed statistically credible.

Although our models do not measure causal effects, log cumulative odds ratios show how the variables on willingness respond to variables of perception and trust or how the associations would vary between genders or age groups. The access to self-reported perceptions provide correlational evidence of which underlying factors could explain a greater willingness. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint 5.6, p<0.001), twice the willing to accept annual vaccination (95%CI=1.6-2.8, p<0.001), and 1.9 times the willing to vaccinate children (95%CI=1.4-2.6, p<0.001) ( Table 1, 

When comparing results between genders, women showed significant associations of all willingness variables with trust in SARS-CoV-2 vaccine (Table S4) . On the other hand, men showed a significant association between willingness to accept the annual vaccination and trust in SARS-CoV-2 vaccine (Table S4) . Interestingly, it was observed in both young people and adults that an increase of trust in SARS-CoV-2 vaccine would induce a higher willingness toward SARS-CoV-2 vaccination, booster dose, annual vaccination and vaccination of children (Table S5) .

The people's trust varied significantly between stakeholders (Kruskal-Wallis test: 2285.9, d.f.=8, p<0.001). Scientists received the highest score of trust among all stakeholders included in the study (Dunn's test with Bonferroni adjustment: z>6.7 and p<0.001 in all comparisons), followed by medical professionals, Chilean Public Health Institute (ISP), and WHO's professionals. The lowest scores of trusts were reported for policy makers and religious leaders. For instance, 63% (n=472) and 28% (n=207) of individuals reported to have a "high" or "pretty trust", respectively, in scientists, and more than 70% of people reported to have a "high" trust (43%, n=323) or "pretty trust" (36%, n=267) in medical professionals. On the contrary, 64% (n=479) and 45% (n=334) of the individuals reported to not trust in religious leaders and policy makers. Factor analysis suggests that the variability of trusts in stakeholders included in the study can be explained by four groups: (a) scientists and medical professionals group, that includes trust in scientists and medical, WHO's, and ISP's is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint [4] ). Interestingly, some groups responded differently to trust in scientists and medical professionals and showed comparatively different associations with the willingness variables. For instance, women did not vary their willingness to accept SARS-CoV-2 vaccine and booster dose, when they reported a higher or lower level of trust in scientists and medical professionals. In contrast, men showed that a higher trust in scientists and medical professionals increased 46.1 and 4.2 times the willingness to accept the SARS-CoV-2 vaccine (95% CI=2.5-862.1, p=0.01) and booster dose (95% CI=1.3-13.1, p=0.02), respectively (Table S4 ). In the case of the willingness to accept the annual vaccination and vaccination of children, both women and men showed a similar positive impact of trust in scientists and medical professionals (Table   S4 ). We found evidence that young and adults differed on how their trust in scientists and medical professionals would impact the variables of willingness. For instance, young people is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint did not vary their willingness to accept the SARS-CoV-2 vaccine, booster dose, annual vaccination, and vaccination of children as their levels of trust in scientists and medical professionals increased (Table S5) . Unlike, adults showed that a higher level of trust increases around three-fold the willingness of SAR-CoV-2 vaccine, booster dose, annual vaccination, and vaccination of children (Table S5 ). In contrast, the results show that willingness to accept both annual vaccination (95%CI=0.6-0.9, p=0.02) and children vaccination (95%CI=0.6-0.9, p=0.004) decreased in 30% as increases one unit of trust in religious leaders ( is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint effective compared with lockdown (Dunn's test with Bonferroni adjustment: z=10.2, p<0.001), but less effective than the use of mask (z=-6.22, p<0.001), washing hands (z=-10.1, p<0.001), physical distance (z=-9.3, p<0.001), avoid meeting people (z=-7.1, p<0.001), and quarantine (z=-3.9, p=0.001). Also, the use of a mask was perceived as less effective than washing hands (z=-4.8, p<0.001) and physical distance (z=-3.3, p=0.011). The lockdown was Most people perceived that the probability of infection with COVID-19 is "little likely" (n=423, 56.8%) or "likely" (n=239, 32.1%) (Fig. 1) . Only 49 individuals (6.6%) of the sample reported that getting COVID-19 is "very likely". In turn, people reported to be "little worried" (n=306, 41%) or "not worried" (n=190, 25.5%) on the side effects of vaccines. A total of 79 individuals of the sample reported to be "very worried" about the side effects of vaccines (n=79, 10.6%) (Fig. 1) .

A score unit higher in the perceived effectiveness of the practices to prevent infection is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. [4] ).

Moreover, we found that associations of willingness variables with perceived effectiveness, perceived infection risk and to be worried about the side effects, varied between genders and cohorts. For instance, when comparing results between genders, women showed significant associations of all willingness variables with perceived effectiveness of prevention practices (Table S4) . On the other hand, men showed a significant association between willingness to accept the annual vaccination and perceived effectiveness of prevention practices (Table S4) .

Analyses across age groups suggest that only adults increased their willingness to accept the booster dose vaccination as their perceived effectiveness of prevention practices increased. Both adults and young people had shown that an increase in perceived effectiveness increased the willingness to accept the annual vaccination and vaccination of children (Table S5) . Also, perception of infection risk was positively and significantly associated with willingness to accept SARS-CoV-2 vaccine (OR=2.4; 95%CI=1.1-5.1; p=0.02) and booster dose (OR=1.7; 95%CI=0.9-3.1; p=0.08) among women, but not among men (Table S4) . To be worry about the side effects decreased the willingness to accept SARS-CoV-2 vaccine both among women (OR=0.5; 95% CI=0.3-0.8, p=0.008) and among men (OR=0.2; 95%CI=0.0-0.9; p=0.03), but only men decreased their willingness to vaccinate children as increase their worry about side effects (OR=0.7; 95%CI=0.5-0.9; p=0.02) (Table S4) showed that a higher worry of side effects decreased the willingness to vaccinate children (OR=0.7, 95%CI =0.6-0.9, p=0.01) (Table S5) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Our results indicate that higher acceptance of the vaccine correlates with a high level of trust in experts of the field (scientists and health workers). Our finding highlights that trust in experts of the field increases the acceptance of SARS-CoV-2 vaccines, booster dose, annual vaccination and vaccination of children. The significant and positive associations emphasize the pivotal role that the trust in experts has on vaccination against COVID-19. In contrast, trust in political or religious leaders is extremely low and on the contrary, when it was high, the refusal to vaccinate was also higher. Our results are consistent with other studies where a high trust in health workers is associated with high acceptance of vaccination 24, 25 . This is also consistent with the lack of trust in vaccine experts who have been associated with support towards political attitudes against vaccines 26 . Our findings also underlined that the trusted information and sources are crucial, suggesting it is not only trust but also confidence in health authorities that affects vaccine acceptance 27 .

The trust in the government has been associated with vaccine acceptance 20 . In the Chilean context, trust in national and health authorities is lower 28 than in other countries 29 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021. 10.31.21265676 doi: medRxiv preprint Our study identified that the older population has a higher acceptance in the vaccination process. Higher acceptance of the vaccine in older populations could be associated with the perception of the risk of contagion of SARS-CoV-2. It has been described that the willingness to be vaccinated is more related to age than to gender, indicating that those who perceive a greater susceptibility to the effects of the virus are more open to accept vaccination and even willing to take a booster dose 29 .

The perception of the risk of the pandemic was initially associated with the older age of those affected, and may be related to the perception of the risk of contagion of the virus, as well as the possibility of protecting their health through vaccination.

According to our results, and in concordance with previous studies, trust in vaccines contributes to explain the acceptance of vaccination uptake 31 Along this line, our findings suggest that in cases where trust in vaccines and the perception of effectiveness were lower, the authorities must have a leading role in developing strategies to convince, to delve into aspects that relate to what should be communicated, and how to increase confidence and education about the vaccine, its characteristics and effects. This is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint aspect is especially important in the Chilean case, but also for many countries worldwide, where the population has been vaccinated with the virion-inactivated Sinovac vaccine.

Consistent with other studies, our results emphasize that to be worried of the side-effects decreases the acceptance of SARS-CoV-2 vaccines 24,33,34 . One of our novel findings for the existing literature is that to be worried of side-effects also decreases the acceptance to vaccinate children, while it does not affect the willingness to accept the booster dose and annual vaccination programs. We also evidence that determinants of willingness to accept vaccination vary between genders and between cohorts. For instance, trust in scientists and medical professionals influences the willingness to accept SARS-CoV-2 vaccine and booster dose only among men and among adults, but not among women or young individuals. The reasons for the gender difference in the trust in scientists and medical professionals are not clear. This can be explained by trust; however, it is not enough to explain the willingness to be vaccinated by women, which should be explored and deepened in further research.

Our findings must be considered in light of some limitations, which we address here. First, we captured different degrees of confidence through an ordinal scale with 4 values, while the variability of confidence may be higher. Second, although we approached different sociodemographic characteristics, it is necessary to consider additional aspects such as cultural, ethnic, rurality and income, among others. Third, given the context of physical distance, the application of the online survey mostly reached those who have constant access to the internet and technological resources, thus excluding people with lower accessibility or knowledge about the internet and technology. Although in these limitations we highlight aspects that must be considered and remedied in future studies, it is necessary to clarify that the present study is consistent and clearly underlined the conditions that propitiate the willingness to accept an annual vaccination, booster doses and the vaccination of children.

In conclusion, our study reports a high intention of the Chilean population to receive a booster dose of the COVID-19 vaccine, annual vaccination and vaccination in children under is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint 16 years of age. Vaccine acceptance is associated with trust in scientists, medical teams and in different media such as television and radio. Perception of risk is a factor that determines in adults the acceptances of vaccination or children vaccination or booster doses.

This study provides the foundations on aspects such as trust and confidence towards COVID-19 vaccination. Other aspects such as information needs, strategies of communications and social media, or interlocutors need to be deepened in future qualitative studies, in which it might be relevant to differentiate the perception of risk in relation to COVID-19 and knowledge of it. The successful acceptance of the vaccination process against COVID-19 in the Chilean population may be useful to establish future strategies, information pathways and vaccination processes that increase the acceptance of vaccines in the population. In this framework, it is essential to continue with investigations that allow to clearly reveal the differences in trust and risk perceptions that are related to COVID-19 vaccination, addressing the subjective particularities that underlie these problems and addressing in a particular way the groups with the greatest reluctance. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint including internal consistency -assessed through Cronbach's Alpha coefficient After this process, the questions were adjusted.

The structured questionnaire was applied through an online platform between May 21 and June 21. With a confidence level of 95% and a confidence interval of 5%, it was estimated that a minimum of 500 people older than 18 years make up a representative sample at the national level. A total of 744 volunteers completed the questionnaire, which were distributed 58% in the Metropolitan region (which concentrates 40% of the national population) and We focused on trust (i) vaccines, (ii) stakeholders, (iii) social media, and (iv) press. To capture the trust in vaccines, the aim was to prompt people to report their trust in each of the vaccines: Sinovac, Pfizer, Cancino, AstraZeneca, Sputnik, and Johnson. We also assessed the trust in different stakeholders, such as scientists, medical professionals, policy makers, religious leaders, relatives and friends. Similarly, we included questions to assess the trust in social media as sources of information, which might influence the willingness to accept vaccines and treatments. Among social media, we asked for the trust in twitter, facebook, instagram, tiktok, whatsapp, and general websites. Last, trust in the press was also included in the questionnaire as formal information sources that might influence individuals, such as is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint national and international newscasts, national and international newspapers, and radio broadcasts. For all questions, we used a 4-value ordinal scale in all questions about trust (from 1=no trust to 4=high trust).

In determining the association to perception variables, the aim was to prompt people to give their thinking about a set of questions about perceptions. First, how individuals perceive the effectiveness of practices to prevent COVID-19 infections was captured through a 4-value ordinal scale, from 1=no effective to 4=high effective. We included the most frequent Chilean prevention practices, such as vaccination, lockdown periods, use of masks, hand washing, social distancing, avoiding meetings, quarantine, and sanitary rooms. Second, we also captured the individual perceived risk of infection in an ordinal scale with four values (from 1=no probable to 4=highly probable). Third, the individual worry on side effects was assessed by a self-reported level of concern using a scale from no-worried (=1) to highly worried (=4). Fourth, we also assessed the perceived understanding of the vaccines of Sinovac, Pfizer, CanSino, AstraZeneca, Sputnik, Johnson, where individuals reported the level of information they considered to have about each vaccine. The individual self-report was assessed using a 4-value ordinal scale (from 1=no information to 4=high information).

Fifth, the individual perception about the plausible relaxation of prevention practices due to vaccination was proxied with the claiming "the vaccination would allow" (i) to relax the use of mask, (ii) to reduce the social distancing, (iii) to avoid COVID-19 infections, (iv) to avoid the severity of COVID-19 illness, and (v) to stop the pandemic. The answer to each practice was captured in a 5-value ordinal scale (from 1=totally disagree and 5=totally agree). Sixth, we evaluate individuals' perceived impact of the COVID-19 pandemic in their quality of life.

We proxied the concept of quality of life with the impact on the job, education, health, income, familial coexistence, and general well-being of the household members. We assessed the impact of the pandemic in a 5-value ordinal scale, from 1=totally negative to 5=totally positive. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint Control variables:

Last, the structured questionnaire included a set of questions to capture control variables that might be associated to the outcome or explanatory variables. We asked whether the respondent or any family member were infected with COVID-19, and whether the illness was acute. We also collected information of age, gender, administrative region of residence, schooling and nationality.

Statistical analysis:

Factor analyses followed by Cronbach's Alpha were carried out to analyze the retained factors and the degree of internal consistency and reliability among variables of trust and perception. We took the average of each factor to create the variables of trust to be included in the multivariate regression analyses.

We were interested in estimating the association between outcome variables of willingness to accept vaccination and explanatory variables of trust and perceptions, while controlling for age, gender, and schooling. We used the following general equation: When the outcome variables were willingness to accept SARS-CoV-2 vaccine, annual vaccines, and vaccination of children, we used ordered logistic multivariate models. In turn, logistic multivariate models were used for when the outcome variable was COVID-19 vaccine booster shot. In all models, we used the same explanatory and control variables. For is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 1, 2021. ; https://doi.org/10.1101/2021.10.31.21265676 doi: medRxiv preprint each outcome variable, we adjusted a set of different models omitting one or more explanatory and control variables. We used the Akaike information criterion (AIC) to perform model comparisons and select the model with the best goodness of fit and parsimony. We ranked the AIC values and defined that the lower AIC value represents the best fitted model (Table S3 ). is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 

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] show results of ordered logit multivariate models. Column [2] shows logit model results. For all columns, cells show odd ratio coefficients and, in parenthesis, confidence intervals at 95%. For each outcome variable, Table shows the model with best goodness of fit and parsimony compared with other candidate models, which was selected using Akaike Information Criterion (see Table S3). * and ** refer to significant levels at 5% and 1%