key: cord-0703944-incyl1q5
authors: MORI, T.; Nagata, T.; Ikegami, K.; Hino, A.; Tateishi, S.; Tsuji, M.; Matsuda, S.; Fujino, Y.; Mori, K.
title: How are sociodemographic factors and risk preferences associated with seasonal influenza vaccination behavior under the COVID-19 pandemic?
date: 2021-05-03
journal: nan
DOI: 10.1101/2021.04.30.21256364
sha: eab697826ccb4877c515b7b5125f887db7546bab
doc_id: 703944
cord_uid: incyl1q5

Background: Vaccine hesitancy is an issue for vaccines required for herd immunity. Although various factors such as sociodemographics can affect vaccine hesitancy, the research results differ and it is unclear whether these differences depend on the subjects or the situation, such as the type of infection or vaccine. Therefore, we investigated the relationship between seasonal influenza vaccination behavior and sociodemographic factors under the COVID-19 pandemic. In addition, we analyzed the relationship between individual factors of risk preference and seasonal influenza vaccination on the premise that there is a difference in the association between efficacy and the risk of side effects of the two vaccines. Methods: A cross-sectional study was conducted on workers aged from 20-65 years on December 22-25, 2020, using data from an Internet survey. We set the presence or absence of 2020/2021 seasonal influenza vaccination as the dependent variable, and each aspect of sociodemographic factors and risk preference as independent variables. We performed a multilevel logistic regression analysis nested by residence. Results: In total, 26,637 respondents (13,600 men, 13,037 women) participated. Significantly more women than men were vaccinated. Both men and women had higher vaccination rates if married, highly educated, with high income, and with underlying disease. Men aged 60-65 had a significantly higher vaccination rate than those aged 20-29, while women aged 40-49 and 50-59 had a significantly lower rate than those aged 20-29. These results differed from those of a previous study on the vaccination intentions of the same subjects for COVID-19. Those with low risk preference had higher vaccination rates than those with high risk preference. Conclusions: Our results suggested that the effect of sociodemographic factors on vaccine hesitancy depends on the situation affecting efficacy of the vaccine and the perception of vaccination risk.

Many vaccines have the effect of preventing infections and aggravation of various infectious diseases, and not only protect the inoculated person but also make a major contribution to the acquisition of herd immunity [1] . However, a significant proportion of people hesitate to accept vaccination and some refuse, which poses a major challenge for vaccine control against infectious diseases [2] . As a background for such vaccine hesitancy, the existence of sociodemographic, psychological, physical, and contextual barriers has been identified [3] and, particularly regarding psychological barriers, many related factors in the explanation and modeling for evaluation, such as the 3Cs (Complacency, Convenience, and Confidence) model [4] and the 5Cs (Confidence, Complacency, Constraints, Calculation, and Collective responsibility) model [5] , have been proposed. These factors include individualspecific factors and environment-dependent factors. Regarding sociodemographic barriers among personal factors, different tendencies have been observed by various studies. For example, women and older adults have both been reported to be vaccination barriers as well as promoters [3] . The basics of psychological barriers can be considered in the context of how to grasp the relationship between vaccination efficacy and risk. Regarding the efficacy of vaccination, the seriousness of the target infectious disease, perception and anxiety about the possibility of infection, and the degree of understanding of the efficacy of the vaccine itself are related [6] . Regarding the risk of inoculation, knowledge about vaccine non-responsiveness [6] and risk preference are related [7] . In this respect, it has been pointed out that there are different gender-specific tendencies regarding risk preference and vaccine inoculation behavior [8] .

So far, with regard to vaccine inoculation at the time of a pandemic, there have been numerous reports on the status of vaccination against the influenza A (H1N1) 2009 virus, reviewed by Brien et al. [9] . At around the same time a few studies compared the 2009/2010 seasonal influenza vaccine inoculation with vaccination for the pandemic [10] [11] [12] . A survey among schoolteachers and staff by Gargono et al. [10] found differences in some psychological variables, although similar factors affected pandemic and seasonal vaccine inoculation and the reasons for vaccinations were the same. By contrast, Vaux et al. [11] reported that there was a difference in inoculation factors between the vaccines, such as that the high risk of infection was not a predictor in the pandemic vaccine. A survey of clinical risk groups with asthma, chronic heart disease, diabetes, etc. by Sammon et al. reported that the pandemic influenza vaccination rate was lower than that of the seasonal vaccine, although similar factors affected both vaccines [12] .

The Coronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 3, 2021. ; https://doi.org/10.1101/2021.04.30.21256364 doi: medRxiv preprint Syndrome Coronavirus 2 (SARS-CoV-2), and the 2020/2021 seasonal influenza vaccination, which was started in the fall of 2020 when the development of the pandemic vaccine was urgently under way, share major symptomatic characteristics. Because the main complaints of influenza are fever and malaise, it is difficult to distinguish it from COVID-19 based on symptoms alone, and to diagnose COVID-19 nucleic acid amplification tests (NAATs), such as real-time reverse transcription-polymerase chain reaction (RT-PCR) or antigen tests, are required [13] . In Japan, although the number of infected people is small in comparison with other countries, the implementation system of tests for diagnosis was insufficient around the fall of 2020. If there was a strong suspicion of a new coronavirus infection after receiving instructions from a public health center or seeing an attending physician, the patient was mandated to undergo tests such as RT-PCR, the results of which were not immediately known [14] . In addition, owing to the small number of infected people, those infected and their close contacts tended to be given special attention. In some cases, the workplace ordered them to remain at home longer than necessary. At the stage when the vaccine against COVID-19 was not yet available, the 2020/2021 seasonal influenza vaccination was recommended for the purpose of preventing influenza, which is difficult to distinguish from COVID-19 [15] . In other words, the expectation for the efficacy of the vaccine is to prevent not only influenza itself but also the possibility of being treated for COVID-19, while the vaccine itself is a seasonal influenza vaccine that has been generally inoculated thus far, with the risk of adverse reactions relatively well known. In such a distinctive situation, examining the factors that contribute to vaccination may provide new insights into vaccine hesitancy.

Using data from an Internet survey conducted on Japanese workers in December 2020 by Fujino et al. [16] , Ishimaru et al. examined the factors that affect the willingness to obtain the COVID-19 vaccine [17] . In this study, we used the same data to analyze the relationship between sociodemographic factors and the 2020/2021 seasonal influenza vaccine intake, and compared our results with those of the previous study. We also examined the association between risk preference and the vaccine intake.

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This cross-sectional study was conducted using data from a baseline study of a prospective cohort study called the Collaborative Online Research on the Novel-coronavirus and Work (CORoNaWork). This survey was conducted as a self-administered questionnaire by Internet research company Cross Marketing (Tokyo, Japan) to investigate the health status of workers from December 22 to December 26, 2020, when the third wave of the COVID-19 pandemic was circulating in Japan. Details of the protocol have already been reported [16] . Participants were workers aged 20 to 65 years at the time of the survey and were stratified by cluster sampling according to gender, age, and region of residence. Participants provided informed consent before answering the questionnaire. After participants with insufficient responses were excluded, 27,036 individuals were enrolled. We then excluded 195 people infected with COVID-19 and 204 who were close contacts, meaning that 26,637 were finally available for analysis. This study was approved by the Ethics Committee of the University of Occupational and Environmental Health, Kitakyushu, Japan (Approval No. R2-079).

Regarding the 2020/2021 seasonal influenza vaccination, we asked participants "Did you receive this season's influenza vaccine?," to which they answered "Yes" or "No."

Regarding risk preference, we asked the question, "When you go out with your family and friends for the first time, how high has the probability of rain to be to take an umbrella?" [18] .

The answer was graded over 10 levels for every 10%, with a probability of precipitation of 0% (always bring a folding umbrella) to 90%. Participants who answered 0% (always bring a folding umbrella) were designated as "Always" and the remaining 10% to 90% were divided into three groups: those who answered from 10% to 30% were defined as "Low risk preference," those who answered from 40% to 60% were defined as "Middle risk preference," and those who answered from 70% to 90% were defined as "High risk preference."

Regarding sociodemographic factors, we investigated gender, age (20-29, 30-39, 40-49, 50-59, and 60-65 years), marital status (single; divorced or widowed; married), education (junior high school or high school; vocational school or college; university or graduate school), . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. ≥8 million JPY), and underlying disease, for which we asked the question, "Do you have any disease that requires regular visits to the hospital or treatment?" Participants selected one of the following: "I do not have such a disease," "I am receiving hospital visits and treatment as scheduled," or "I am not receiving hospital visits and treatment as scheduled." We rated the participants who answered, "I do not have such a disease" as "No" and the remaining two answers as "Yes."

Seasonal influenza vaccination rates were calculated for all variables and further for each gender. We set the presence or absence of 2020/2021 seasonal influenza vaccination as the dependent variable, and each aspect of sociodemographic factors consisting of gender, age, marital status, education, annual household income, and treatment history as independent variables. We performed age-adjusted multilevel logistic regression analysis for each independent variable. In addition, given that gender is an important factor in vaccination, the same analysis was performed for each gender. Furthermore, to investigate the relationship between risk preference and influenza vaccination, with the presence or absence of 2020/2021 seasonal influenza vaccination as the dependent variable and risk preference as the independent variable, we performed multilevel logistic regression analysis for each gender adjusted for age (Model 1) and adjusted for sociodemographic factors with occupation (Model 2). Considering the influence of regional differences in the infection status of COVID-19 and the inoculation status of conventional seasonal vaccines, all analyses were performed by multilevel analysis nested by prefecture of residence. Adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) were calculated, and P values of less than 0.05 were considered statistically significant. All analyses were performed using STATA Version 16 (StataCorp, College Station, TX, USA).

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Significantly more women than men were vaccinated (aOR 1.34, 95% CI 1.27-1.42). The vaccination rate was lower in older people than in younger people, and more married people were vaccinated than single people. In addition, more vaccinations were administered to those with higher education, higher annual household income, and with underlying disease ( Table 2) .

The results by gender showed that the inoculation rate was significantly higher in men aged 60-65 than in the age group 20-29 (aOR 1.62, 95% CI 1.18-2.23). There was no significance among those aged 30-39, 40-49, and 50-59, but the OR was high compared with those aged 20-29. In women, however, the vaccination rate was significantly lower in those aged 40-49 and 50-59 than in those aged 20-29 (aOR 0.78, 95% CI 0.69-0.87/aOR 0.76, 95% CI 0.67-0.85). For other variables, the results were similar for both men and women (Table 3) .

The results of adjusting for age (Model 1) and of adjusting for all sociodemographic factors (Model 2) were similar. In Model 2, the vaccination rate was significantly higher in men in all . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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Vaccine hesitancy is defined by a working group of a World Health Organization advisory body (Strategic Advisory Group of Experts on Immunization, SAGE) as "delay in acceptance or refusal of vaccines despite availability of vaccine services. Vaccine hesitancy is complex and context specific, varying across time, place and vaccines. It is influenced by factors such as complacency, convenience and confidence" [19] . Because vaccination is an effective means for infectious disease control and is indispensable for the acquisition of herd immunity, the existence of such vaccine hesitancy is a major issue in infectious disease control [2] . Many studies have pointed out that various influential factors have an effect on vaccine hesitancy. The present study, performed at the time of the spread of the COVID-19 pandemic, targets vaccination behavior in special situations that have not been experienced so far, namely that it is difficult to distinguish influenza from COVID 19 on the basis of initial symptoms and that, given this may impose a burden on the medical system, seasonal vaccination was recommended to help prevent such a situation. In addition, it is possible to compare the already reported effects of COVID-19 vaccine with the intention to be inoculated [17] . Therefore, the purpose of our study was to provide new findings for research into vaccine hesitancy.

As a sociodemographic factor, the female vaccination rate is higher, and the results of analysis by gender show that the vaccination rate among men is higher in older adults, married people, highly educated people, high-income earners, and those with underlying disease. In women, the inoculation rate was higher for younger respondents, but other factors were the same as in men. Regarding the relationship between inoculation behavior and risk preference, risk aversion was higher in both men and women, although the OR for high risk preference was higher for men.

Schmid et al. [3] reviewed papers from the period 2005-2016 covering the factors that influence influenza vaccine inoculation. Of these, regarding sociodemographic factors it has been identified that gender and age could be both barriers and promoters. In addition, it has been reported that living alone, not being married, and having no diseases under treatment led to non-vaccination, while history of marriage was consistent with our current results. Brien et al. [9] reviewed papers on the inoculation tendency for the A/H1N1 influenza vaccine during that pandemic in 2009. Here the results differed among reports depending on gender and age, while regarding educational background, five out of seven reports concluded that higher education promoted vaccination. The presence of chronic diseases has also been highlighted as a promoter of vaccination. As described above, there have been conflicting reports on the relationship between sociodemographic factors such as gender and age and vaccination . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 3, 2021. ; https://doi.org/10.1101/2021.04.30.21256364 doi: medRxiv preprint behavior, but it is not clear whether such an association depends on the characteristics of the target population or the status of infection and regional effects.

The 2020/2021 seasonal influenza vaccine has been a major feature during the outbreak of COVID-19. With regard to seasonal influenza vaccination at the time of a pandemic outbreak, one study focused on the faculty and staff of middle and high schools in the United States when the 2009 H1N1 influenza occurred, whereby more inoculations of both the seasonal vaccine and 2009 H1N1 influenza vaccine were administered to men, and there was no difference in the effects of demographic variables between the two vaccines [10] . A study from France found that both the seasonal vaccine and 2009 H1N1 influenza vaccine showed lower vaccination rates in adults under the age of 30 years and no difference in gender between the two vaccines [11] . It was reported that for the seasonal influenza vaccine, when the head of the household was a junior college graduate, the vaccination rate was lower than that of high school graduates and university graduates, while for the pandemic influenza vaccine the rate was higher among university graduates than in those with low education. In addition, a study among clinical risk groups in the United Kingdom reported that women were less likely to receive the 2009 H1N1 influenza vaccine, although gender was not associated with seasonal influenza vaccination.

Moreover, uptake of both vaccines differed significantly across different age groups. While receiving the seasonal vaccine was increasing in each age category from childhood up to 65-to 80-year-olds, receiving the pandemic vaccine was bimodal, with the highest uptake rates achieved in those aged 6 months to 5 years and in those aged 40-64 years [12] . Thus, although different results have been reported, overall the effects of sociodemographic factors on inoculation with seasonal vaccines and pandemic vaccines were similar in the same subjects.

In a study conducted by Ishimaru et al. on the COVID-19 vaccination intentions of the same subjects as in our study, women were less willing than men to be vaccinated, and a genderspecific analysis showed that older women were more willing and highly educated women less willing to be vaccinated [17] . In other words, in women the association between sociodemographic factors and inoculation was different from our results for seasonal influenza vaccine. However, the same result was obtained for men. From the aforementioned, we speculate that some groups of women have different inoculation behaviors with regard to the COVID-19 vaccine and the seasonal influenza vaccine.

Risk perception has a great influence on vaccination intention and comprises three dimensions: perceived likelihood, perceived severity, and perceived susceptibility. A metaanalysis of 34 papers, including studies on influenza vaccines, showed that the higher is each dimension, the greater is the number of vaccinations [20] . The reviews of influenza vaccine . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 3, 2021. ; https://doi.org/10.1101/2021.04.30.21256364 doi: medRxiv preprint studies have reported that perceived severity of the disease and perceived susceptibility to the disease affect vaccination [3] . From our results, we considered that more subjects with underlying disease were vaccinated because of the perceived susceptibility of these three dimensions. However, vaccination decisions will not only be made through risk perception of infection but also by comparing the positive and negative aspects of vaccination, such as efficacy of the vaccine and the risks of side effects [6] .

In other words, efficacy is affected by the combination of potential efficacy and the severity of the disease or situation, while the risk of vaccination can be assessed by the combination of severity of side effects and likelihood of occurrence, and a high perceived risk of adverse events from vaccine can decrease vaccine uptake. Thus, vaccination behavior will depend on the situation as well as risk perception.

The main characteristic of the 2020/2021 seasonal influenza vaccine was that perceived efficacy did not involve merely the prevention of influenza. If contracting influenza it was necessary to consult a medical institution or contact a health center in a situation whereby it was difficult to distinguish influenza from COVID-19, complicated by problems that occurred in the diagnostic process and results. At the time of the survey in Japan, where the number of infected people was smaller than in Western countries and the establishment of testing systems such as RT-PCR was delayed, it took time to make a definitive diagnosis [14] and there was also prejudice against infected people. According to ISO 31000 [21] , the international standard for risk management, risk is the effect of uncertainty on various purposes, and uncertainty is an important factor in risk assessment. Specifically, the higher the uncertainty, the higher is the risk perception. The annual influenza vaccination rate for the Japanese population is reported to be around 30%-40% for adults under the age of 65 years [22, 23] , and in this study conducted in December the vaccination rate was already slightly higher than was stated in these reports. This may be due to the relatively high risk of contracting seasonal influenza, resulting in increased perception of vaccine efficacy.

Risk preference in decision making is another factor that can influence an individual's vaccination behavior. Risk preference is one of the indicators of behavioral economics by which humans sometimes make irrational decisions owing to the intertwining of various biases, and is generally used to assess risk attitudes, whereby those with low risk preference tend to behave in a risk-averse manner [24] . In the area of health behavior, it has been reported that smokers also have a higher risk preference: they do not measure their blood pressure, do not use floss to brush their teeth, and have more accidents at work or at home than non-smokers [25] . It has also been reported that risk aversion is negatively associated with cigarette smoking, heavy . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 3, 2021. ;  drinking, being overweight or obese, and non-use of seat belts [24] .

The impact of risk aversion has been reported to be context dependent, with risk-averse people less likely to undergo breast cancer screening because of the further risk that if the cancer is found and treated, such treatment may fail [26] . Our results suggest that the lower the risk preference, the higher is the vaccination behavior, arising from recognition of the greater risk of non-vaccination against the background scenario that the vaccine is highly effective. In addition, regarding risk preference and vaccination, a positive relationship between risk aversion and the demand for influenza vaccine has been reported [18] . However, there are gender differences in this relationship, with risk preference being positively associated with vaccination behavior in men but not in women [8] . Our results showed that women had lower ORs than men, but women could have similar relationships, indicating that risk preference could affect vaccination in women although to a lesser extent than in men, which is a new finding. In addition, although the analysis results were not shown in this paper, no similar effect was observed on the COVID-19 pandemic vaccine. Such risk preference may affect the vaccination behavior of COVID-19 and seasonal vaccines, especially in women. Risk preference is generally measured by asking whether to bring an umbrella according to the probability of rain, as in this study, or whether or not to participate in the lottery based on the probability of winning and the amount of money, an approach also used in vaccine research [8, 18] . We used the question about bringing an umbrella because more people are familiar with it.

However, among the options for this question, the respondents who "always go out with a folding umbrella" may include those who have a habit of always putting them in their bags regardless of their risk preference. This may have led to the possibility that this option had a significant but small effect in men and no significant difference in women.

In any case, this study showed that the relationship between vaccination behavior and sociodemographic factors for two vaccinations based on information taken simultaneously for the same population differs between the two vaccines, and the results suggest that the effects of sociodemographic factors on vaccine hesitancy are situation dependent and centered on the relationship between vaccination efficacy and risk.

There were several limitations to this study. First, because we conducted an Internet survey, selection bias might have occurred. Although we stratified by cluster sampling according to gender, age, and region of residence at the beginning of the survey to reduce bias, the survey was intended for people registered as an online survey panel and was not representative of the . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 3, 2021. ;  general population. Second, regarding influenza vaccination, we asked subjects whether they were vaccinated between December 22 and 26 in 2020, when the survey was conducted; therefore, those who were vaccinated after that time and those scheduled to be vaccinated were not included. In particular, the 2020/2021 influenza vaccine has been in short supply in some areas and medical institutions owing to high demand for vaccination because of the influence of the COVID-19 pandemic, and in some cases there was a long waiting time before inoculation.

However, since vaccination started at the end of October in Japan, it was probable that those who had decided to be inoculated had collected information on supply shortages and made reservations and vaccinations early. Furthermore, regarding risk preference, we adopted a common evaluation question that is often used but, because there was only one question, detailed evaluation was difficult. Third, although it has been pointed out that vaccine hesitancy can be affected by various psychological factors, there might be some items that could not be adjusted. Fourth, the COVID-19 vaccine was intended for inoculation, whereas the 2020/2021 influenza vaccine, which was the subject of this study, had already been inoculated and could not be directly compared.

We collected data on two vaccination regimes, COVID-19 vaccine and 2020/2021 seasonal influenza vaccine, at the same time in the same population under the COVID-19 pandemic. We found differences in the relationship between vaccination behavior and sociodemographic factors, particularly regarding the impact of risk preference. Our results suggest that the effect of sociodemographic factors on vaccine hesitancy depends on the situation affecting the perception of vaccine efficacy and inoculation risk. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 3, 2021. ; 

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We thank the current members of the CORoNaWork Project, in alphabetical order, are as follows: Dr. Yoshihisa Fujino (present chairperson of the study group), Dr. Akira Ogami, Dr. 

Competing Interest: None declared.