(2022) 22:126
Sekizawa et al. BMC Public Healthhttps://doi.org/10.1186/s12889-021-12479-w

Open Access

RESEARCH

Association between COVID-19 vaccine
hesitancy and generalized trust, depression,
generalized anxiety, and fear of COVID-19
Yoichi Sekizawa1*, Sora Hashimoto2, Kenzo Denda3, Sae Ochi4 and Mirai So5

Abstract
Background: Although numerous studies have been published on the predictors of COVID-19 vaccine hesitancy,
some possible predictors remain underexplored. In this study, we explored the associations of unwillingness andindecisiveness regarding COVID-19 vaccination with generalized trust, mental health conditions such as depression
and generalized anxiety, and fear of COVID-19.
Methods: Data of wave 1 (from October 27 till November 6, 2020) and wave 3 (from April 23 till May 6, 2021) of alongitudinal online study conducted in Japan were used for the analyses. Unvaccinated participants were asked atwave 3 about their willingness to be vaccinated, with possible responses of willing, unwilling, or undecided. These
three responses were used as the outcome variable, and multinomial logistic regression analyses were conductedwith willingness to be vaccinated as the reference group. Explanatory variables included generalized trust, depression,
generalized anxiety, and fear of COVID-19 both at wave 1 and 3, and sociodemographic and health-related variables.
Results: Of the 11,846 valid respondents, 209 (1.8%) answered that they had already been vaccinated against
COVID-19, 7089 (59.8%) responded that they were willing to be vaccinated, 3498 (29.5%) responded that they were
undecided, and 1053 (8.9%) responded that they were unwilling to be vaccinated. After adjusting for covariates, wefound that: (1) participants with lower levels of generalized trust at wave 1 and 3 were more likely to be undecided or
unwilling at wave 3; (2) respondents with moderately severe or severe depression at wave 1 and 3 were more likely
to be undecided at wave 3; (3) participants with moderate or severe levels of generalized anxiety at wave 3 but not atwave 1 were more likely to be unwilling at wave 3; and (4) respondents with high levels of fear of COVID-19 at wave 1
and 3 were less likely to be undecided and unwilling at wave 3.
Conclusions: Generalized trust, mental health conditions such as depression and generalized anxiety, and low levelof fear of COVID-19 are associated with unwillingness or indecision regarding being vaccinated against COVID-19.
Keywords: COVID-19, Vaccine hesitancy, Generalized trust, Depression, Generalized anxiety, Fear of COVID-19
Background
COVID-19 has been prevalent around the world since
the end of 2019, and many people have lost their lives
due to this infectious disease. Many countries have*Correspondence: sekizawa-yoichi@rieti.go.jp
1
Research Institute of Economy, Trade and Industry, Chiyoda‑ku,
Kasumigaseki 1‑3‑1, Tokyo 100‑8901, Japan
Full list of author information is available at the end of the article

implemented strict measures to control the spread ofthe disease, such as lockdowns and mandatory wearingof face masks; despite these measures, the disease has
spread across the world.
Vaccination is one of the most effective ways of halting the spread of COVID-19. Several vaccines havebeen developed over a short period of time. Vaccination not only helps prevent individual infections, but© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of thislicence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​
mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Sekizawa et al. BMC Public Health(2022) 22:126

mass vaccination prevents medical resources frombeing overwhelmed by lowering the number of critically ill patients and has the potential to halt the pandemic through the achievement of herd immunity. As
of November 27, 2021, almost half of the global population has received at least one dose of the COVID19 vaccine, and more than 7 billion doses have been
administered worldwide [1].
Vaccine hesitancy has been defined as a “delay inacceptance or refusal of vaccination despite availabilityof vaccination services” [2]. It creates a serious problem
in the promotion of vaccination against COVID-19 [3].
Despite the importance of vaccination, many people are
known to have a negative attitude toward it [4]. There isa concern that even if a vaccination program progresses
initially, it may stall at some point because of the large
number of people in many countries who refuse to be
vaccinated [5]. An exploration of the type of people whoare less likely to receive a vaccine against COVID-19 isimportant in order to cover maximum range of people
with vaccination. Numerous studies that address thequestion of which people were reluctant to be vaccinatedhave been published recently [6–23]. Most of these studies showed that younger people [7, 8, 12, 14–16, 19–23],
women [6, 7, 9–12, 14–16, 19–23], people with low
incomes [6, 11, 13–15, 18, 19, 21, 22], and people withlower levels of education [6, 7, 10, 11, 13–16, 18–23] werereluctant to receive a vaccine.
Although many predictors of vaccine hesitancy
have been identified, some possible predictors remain
underexplored. Of these, we examined the associations
between vaccination hesitancy and generalized trust,mental health factors such as depression and generalized
anxiety, and fear of COVID-19.
Specific trust, such as trust in vaccines, the government, the health system, or professionals, has been sufficiently explored in the context of vaccine hesitancy ingeneral [24, 25], and specifically for COVID-19 vaccines(trust in vaccines [6, 16, 26–28], trust in government [20,22, 26, 29, 30], trust in healthcare system or practitioners [16, 31–33]). By contrast, generalized trust, i.e., adefault expectation of goodwill from other people [34]that is often viewed as an important part of social capital [35], has not been sufficiently explored in the context
of vaccine hesitancy. We are aware of two studies that
focus on the association between generalized trust and
COVID-19: Frank and Arim [36] and Ahorsu et al. [31].
Both reported that those who indicated higher levels ofgeneralized trust tended to be more willing to receive
the COVID-19 vaccine than those with lower levels ofgeneralized trust. Regarding the association between
generalized trust and vaccine hesitancy other than for
COVID-19, we found three studies, and all of them

Page 2 of 17

concluded that generalized trust was associated withhigher willingness to receive a vaccine against influenza[37–39].
Similar to generalized trust, studies that explore theattitudes of people with mental illness toward vaccination
against COVID-19 are scarce [40] and inconsistent. To
our knowledge, there have been five studies in the UnitedStates, China, Germany, and Japan [15, 17, 22, 41, 42].
Three of them found no significant association between
depression/anxiety and vaccine hesitancy [15, 17, 41]. By
contrast, a study in China that concentrated on people
with children found that psychologically distressed subjects were more likely to have vaccine hesitancy related
to themselves, their spouses, and their children [42].
Similarly, a study in Japan showed that respondents withsevere psychological distress were more likely to havevaccine hesitancy related to the COVID-19 vaccines[22]. More broadly, studies that explore the relationshipbetween depression/anxiety and vaccine hesitancy ingeneral suggest that those who have depression/anxiety
tend to be willing to be vaccinated mostly for influenza[43–45].
Regarding fear of COVID-19, several studies havealready explored the association between fear of COVID19 and vaccine hesitancy [15, 22, 26, 27, 41, 46–48]. All ofthem except one [46] found that fear of COVID-19 was
positively associated with willingness to be vaccinatedagainst COVID-19. More broadly, studies that exploredthe relationship between the willingness to receive vaccination and the fear of the disease the vaccine prevents
concluded that those who fear the disease tend to be
more willing to be vaccinated [49–53]. Nevertheless, arecent model study on the COVID-19 vaccine suggested
that the impact of the fear of COVID-19 on the willingness to receive vaccination is small, although it exists[54]. Against this background, it is worthwhile to confirm the robustness of the association between fear of
COVID-19 and the willingness to receive vaccination ina country like Japan where the prevalence of COVID-19
cases was lower than in most other countries [1].
In the present study, we explored two things. First, we
explored whether generalized trust, mental health factors such as depression and generalized anxiety, and fearof COVID-19 were predictors of COVID-19 vaccine
hesitancy. Second, we explored whether the results of theprevious studies on predictors, in particular socioeconomic ones, of vaccine hesitancy against COVID-19 canbe confirmed with a large data of Japanese people.

Methods
Research design, participants, and procedures

A longitudinal online survey named “Continuing survey
on mental and physical health during the COVID-19

Sekizawa et al. BMC Public Health(2022) 22:126

pandemic” (hereinafter “RIETI questionnaire survey”)
was planned and organized by the authors as part of a
research project of the Research Institute of Economy,
Trade and Industry, Japan (RIETI). This longitudinal survey was conducted by NTTCom Online Marketing Solutions Corporation based on the design and instructionsof the authors. We used wave 1 and wave 3 of the RIETI
questionnaire survey for the present study. Wave 1 was
conducted from October 27 to November 6, 2020. Wave
3 was conducted from April 23 to May 6, 2021. Study
participants were recruited from the registrants of thecorporation or its affiliates. The participants at wave 1
were men and women aged 18–74 years living in Japan.
They were extracted so that their demographic composition ratios of sex, age, and distribution of residential
prefectures matched the population estimates of the Statistics Bureau of Japan (final estimates, May 2020). Data
were excluded for individuals who provided non-existent
zip codes, zip codes that did not match their previously
registered prefectures, extreme outlying values for height
and weight among Japanese adults (2 m or taller andweight lower than 35 kg or in excess of 100 kg, measurements that are outside the national average in Japan), orage differing by 2 years or more from the age previously
registered. Respondents who took a very short time (lessthan 5 min) or a very long time (10 h or more) to answer
the survey questions were also excluded. The remaining
number of individuals after these exclusions was 16,642(8022 men, 8620 women) and they were established asvalid respondents for wave 1. In the subsequent waves,
we asked all valid respondents from wave 1 to respond to
the surveys by email. For wave 3, those who took a very
short time (less than 4 min) or a very long time (10 h ormore) to answer the survey questions were excluded. All
communication with study participants, including thequestionnaires, was conducted in Japanese.
All individuals who participated in this study provided
online informed consent for their participation. The present study was conducted with the approval of the ethics committee of Hiramatsu Memorial Hospital (No:20200925). All methods were carried out in accordancewith relevant guidelines and regulations.
Outcome variables

The outcome variables used in the present study werebased on the following two questions regarding vaccination against COVID-19, which were asked only in wave
3. The first question asked whether the respondent had
been vaccinated. If participants had received at least one
dose, they were treated as having been vaccinated. The
second question was asked only of those who had notbeen vaccinated. The question was: “Are you going toreceive a vaccine against COVID-19?” It was scored asPage 3 of 17

willing to be vaccinated, unwilling to be vaccinated, or
undecided.
Explanatory variables
Generalized trust, depression, generalized anxiety, and fearof COVID‑19

To measure generalized trust, we used the Japanese version of the following question from the World Values
Survey (WVS) Wave 6 [55]: “Generally speaking, would
you say that most people can be trusted or that you need
to be very careful in dealing with people?” The available
answers were as follows: “Most people can be trusted,”“Need to be very careful,” and “Don’t know.” Respondents
who selected “Need to be very careful” and “Don’t know”
were regarded as having low generalized trust. This question has been validated by two experimental studies [56,57].
Depression was measured using the Patient Health
Questionnaire-9 (PHQ-9) [58]. The PHQ-9 is a nineitem self-administered questionnaire designed to assess
the presence and severity of depressive symptoms during the past 2 weeks. Example items include “little
interest or pleasure in doing things” and “feeling down,
depressed, or hopeless.” The answers in the PHQ-9 consist of a four-point scale ranging from 0 (not at all) to 3
(nearly every day). The PHQ-9 scores range from 0 to 27,
with higher scores indicating progressively more severe
depression (0–4 = no depression, 5–9 = mild depression, 10–14 = moderate depression, 15–19 = moderately severe depression, and 20–27 = severe depression).
Although the original version of the PHQ-9 is in English,
a Japanese version was used in the present study [59]. The
Japanese version of PHQ-9 has been validated by Muramatsu et al. [60].
Anxiety was measured by means of the Generalized
Anxiety Disorder-7 scale (GAD-7) [61]. The GAD-7 isa seven-item, self-administered questionnaire that isdesigned to measure generalized anxiety symptoms during the past 2 weeks. Example items include “feelingnervous, anxious, or on edge” and “not being able to stopor control worrying.” The answers in the GAD-7 consist of a four-point scale ranging from 0 (not at all) to 3
(nearly every day). The GAD-7 scores range from 0 to 21,
with higher scores indicating progressively greater levelsof anxiety (0–4 = minimal anxiety, 5–9 = mild anxiety,10–14 = moderate anxiety, and 15–21 = severe anxiety).
Although the original version of the GAD-7 is in English,
a Japanese version was used in the present study [62].
The Japanese version of GAD-7 has been validated by its
translators [62].
The Fear of COVID-19 Scale (FCV-19S) was used tomeasure fear related to COVID-19 [63]. The FCV-19S
is a seven-item, self-reporting questionnaire designed toSekizawa et al. BMC Public Health(2022) 22:126

measure the extent to which a person fears COVID-19.
Example items included “I am most afraid of coronavirus-19” and “it makes me uncomfortable to think aboutcoronavirus-19.” The answers in the FCV-19S consist ofa five-point scale ranging from 1 (strongly disagree) to 5
(strongly agree). The FCV-19S scores range from 7 to 35,
with higher scores indicating progressively greater levelsof fear related to COVID-19. Since there were no clear
categories for the FCV-19S scores, we defined them asfollows: 7–15 = no fear, 16–20 = mild fear, 21–25 = moderate fear, and 26–35 = severe fear. Although the original
version of the FCV-19S is in English, a Japanese version
was used in the present study [64]. The Japanese version
of FCV-19S has been validated by its translators [64].
Other explanatory variables

Sociodemographic variables included sex, age, level of
education, family members living together, employment status, annual household income, bank and saving deposit amount, and place of residence (individual
prefectures with a population of 5 million or more [nineprefectures], and eight regions of Japan for those living
in other prefectures). Marital status was not included
because the question regarding family members living
together was similar. For variables relating to health, weused body mass index (BMI) and whether pre-existing
conditions (hypertension, dyslipidemia, diabetes, heartdisease, renal disease, cancer, respiratory disease, andother) were present. Descriptions of the explanatory variables are shown with the basic statistics in Table 1.

Page 4 of 17

and saving deposit amounts in Models 1 and 2 at wave
1 and wave 3 were those at wave 1 and 3, respectively.
Remaining explanatory variables were those at wave 1.
For all models we calculated the relative risk ratio (RRR)
and the 95% confidence interval. Statistical analyses werecarried out using STATA 15.0 (STATACorp LLC, Texas,
USA).

Results
Study participants and characteristics

In wave 3, we sent surveys via email to the 16,642 valid
respondents from wave 1, and the total number of
responses was 13,279 (79.8%). After excluding those who
took a very short time (less than 4 min) or a very longtime (10 h or more) to answer the survey questions, thenumber of valid respondents was 11,846 (5965 males
and 5881 females), and the mean age was 54.0 years(SD = 14.2 years). The basic statistics for the outcome
variables and all explanatory variables are presented inTable 1.
Attitude toward vaccination

Of the 11,846 valid respondents, 209 (1.8%) answeredthat they had already been vaccinated against COVID19, 7089 (59.8%) responded that they were willing to be
vaccinated, 3498 (29.5%) responded that they were undecided, and 1053 (8.9%) responded that they were unwilling to be vaccinated (Table 1).

Statistical analysis

Association of generalized trust, depression,
generalized anxiety, and fear of COVID‑19 with attitudes
toward vaccination against COVID‑19

Descriptive statistics were presented with frequency andpercentages for categorical variables. Continuous variables were grouped into categorical variables (e.g., age,
BMI, household income). Multinomial logistic regression analyses were conducted to estimate the associations
between the explanatory variables and the outcome variables. Respondents willing to receive a vaccine at wave 3(reference group) were compared with (1) those who were
undecided regarding vaccination; and (2) those who were
unwilling to be vaccinated. We estimated four models. In
Model 1 at wave 1 and Model 1 at wave 3, the explanatory
variables of primary interest were any one of generalized
trust, depression (PHQ-9), generalized anxiety (GAD-7),
and fear of COVID-19 (FCV-19S) experienced during
wave 1 and wave 3, respectively. In Model 2 at wave 1 andModel 2 at wave 3, the explanatory variables of primaryinterest were all of generalized trust, PHQ-9, GAD-7, andFCV-19S together, at wave 1 and wave 3, respectively. Allother explanatory variables were adjusted for in all models. Generalized trust, PHQ-9, GAD-7, FCV-19S, age,
employment status, annual household income, and bank

Table 2 presents the results of the adjusted multinomial
logistic regression analyses focusing on the associationof generalized trust, depression, generalized anxiety, andfear of COVID-19, with attitudes toward vaccination
against COVID-19.
Regarding generalized trust, Model 1 at wave 1 andwave 3 both showed that those who answered “Need tobe very careful” and “Don’t know” were more likely to
be undecided, or unwilling to be vaccinated, than those
who answered “Most people can be trusted.” The results
were basically the same in Model 2 at wave 1 and wave
3, in which depression, generalized anxiety, and fear of
COVID-19 were adjusted for.
Regarding depression, Model 1 at wave 1 and wave 3
both showed that those who were mildly depressed,
moderately depressed, moderate-severely depressed,
and severely depressed were more likely to be undecided
than those who were not depressed. These results werebasically the same in Model 2 at wave 1 and wave 3, in
which generalized trust, generalized anxiety, and fearof COVID-19 were adjusted for, except that mild andSekizawa et al. BMC Public Health(2022) 22:126

Page 5 of 17

Table 1 Characteristics and vaccine-related attitudes of study participants
Predictors

Overall sample

Already vaccinated209 (1.8%)

Not vaccinatedTotal

Willing

Undecided

Unwilling

7086 (59.8%)3498 (29.5%)1053 (8.9%)

11,846Sex
Male

102 (1.7%)

3778 (63.3%)

1583 (26.5%)

502 (8.4%)

5965

Female107 (1.8%)3308 (56.2%)

1915 (32.6%)551 (9.4%)

5881

Age group, years at wave 1
65+

28 (0.9%)2377 (80.1%)422 (14.2%)

142 (4.8%)

2969

50–64

72 (1.7%)

2696 (61.8%)

1262 (28.9%)

330 (7.6%)

4360

30–49

77 (2.2%)

1615 (46.9%)

1347 (39.1%)

402 (11.7%)

3441

18–29

32 (3.0%)398 (37.0%)

467 (43.4%)

179 (16.6%)

1076

Age group, years at wave 3
65+

30 (1.0%)2482 (79.8%)451 (14.5%)

148 (4.8%)

3111

50–64

74 (1.7%)

2671 (60.9%)1296 (29.5%)345 (7.9%)

4386

30–49

78 (2.3%)

1573 (46.6%)1330 (39.4%)

394 (11.7%)

3375

18–29

27 (2.8%)360 (37.0%)

421 (43.2%)

166 (17.0%)974

Highest education
Junior/senior high school

30 (0.8%)2171 (57.2%)

1215 (32.0%)378 (10.0%)

3794

Two- or three-year college

67 (2.6%)

1446 (57.0%)

779 (30.7%)245 (9.7%)

2537

Four-year college or higher

112 (2.0%)3469 (62.9%)1504 (27.3%)

430 (7.8%)

5515

Family members living together at wave 1
Living alone

40 (2.0%)1043 (52.7%)657 (33.2%)

241 (12.2%)

1981

Living only with spouse45 (1.3%)

2479 (71.3%)

757 (21.8%)

198 (5.7%)

3479

Living with children

79 (2.2%)

2181 (60.8%)1056 (29.4%)

274 (7.6%)

3590

Living with parents

28 (1.4%)

972 (48.3%)

756 (37.6%)

256 (12.7%)

2012

Three-generation household

14 (2.3%)

324 (54.4%)

205 (34.4%)

53 (8.9%)596

Other (siblings only, friends, grandparents 3 (1.6%)
and grandchildren etc.)

87 (46.3%)

67 (35.6%)

31 (16.5%)

188

Employment at wave 1
Employed

184 (2.6%)4043 (57.5%)

2163 (30.7%)646 (9.2%)

7036

Homemaker

11 (0.5%)

1491 (64.8%)659 (28.6%)

141 (6.1%)

2302

Not employed (seeking a job)

3 (1.0%)140 (47.9%)

109 (37.3%)

40 (13.7%)292

Not employed (not seeking a job)

6 (0.3%)1250 (68.6%)

399 (21.9%)

166 (9.1%)

1821

Student

5 (1.9%)98 (37.1%)

121 (45.8%)

40 (15.2%)

264

Other

0 (0.0%)64 (48.9%)47 (35.9%)

20 (15.3%)

131

Employment at wave 3
Employed

185 (2.6%)4023 (57.1%)

2199 (31.2%)

639 (9.1%)

7046

Homemaker

13 (0.6%)

1475 (65.0%)646 (28.5%)

134 (5.9%)2268

Not employed (seeking a job)

2 (0.6%)159 (51.1%)

101 (32.5%)

49 (15.8%)311

Not employed (not seeking a job)

7 (0.4%)

1278 (68.4%)

407 (21.8%)

176 (9.4%)

1868

Student

2 (0.9%)85 (39.4%)

97 (44.9%)

32 (14.8%)

216

Other

0 (0.0%)66 (48.2%)

48 (35.0%)

23 (16.8%)

137

Annual household income, million yen at wave 1<3

35 (1.2%)

1611 (53.2%)

1013 (33.4%)

372 (12.3%)

3031

3–4

42 (1.3%)

2071 (63.6%)

872 (26.8%)

269 (8.3%)

3254

5–7

68 (2.2%)

1887 (59.7%)

981 (31.0%)225 (7.1%)

3161

≥8

64 (2.7%)

1517 (63.2%)

632 (26.3%)

187 (7.8%)

2400

Annual household income, million yen at wave 3<3

32 (1.0%)1680 (54.3%)

1008 (32.6%)

372 (12.0%)

3092

3–4

45 (1.4%)2024 (62.8%)888 (27.5%)

267 (8.3%)

3224

Sekizawa et al. BMC Public Health(2022) 22:126

Page 6 of 17

Table 1 (continued)
Predictors

Already vaccinatedNot vaccinatedWilling

Total
Undecided

Unwilling

5–7

67 (2.1%)

1885 (59.6%)

988 (31.2%)

224 (7.1%)

3164

≥8

65 (2.7%)

1497 (63.3%)

614 (26.0%)

190 (8.0%)

2366

Bank and savings deposit amount, million yen at wave 1<1

63 (2.0%)1529 (49.5%)1121 (36.3%)

373 (12.1%)

3086

1–3

39 (1.7%)

1286 (56.5%)

743 (32.6%)

209 (9.2%)

2277

4–9

47 (2.0%)1421 (60.0%)706 (29.8%)

196 (8.3%)

2370

≥ 10

60 (1.5%)2850 (69.3%)

928 (22.6%)

275 (6.7%)

4113

Bank and savings deposit amount, million yen at wave 3<1

51 (1.6%)

1538 (49.1%)

1153 (36.8%)

390 (12.5%)

3132

1–3

51 (2.3%)

1258 (56.8%)

714 (32.2%)

191 (8.6%)

2214

4–9

39 (1.7%)

1417 (61.1%)

687 (29.6%)

176 (7.6%)

2319

≥ 10

68 (1.6%)2873 (68.7%)

944 (22.6%)

296 (7.1%)

4181

BMI at wave 1< 18.523 (1.6%)739 (50.4%)524 (35.7%)

181 (12.3%)

1467

18.5–24.9

148 (1.8%)4930 (60.5%)2377 (29.2%)

693 (8.5%)8148

25.0–29.9

32 (1.7%)

1210 (64.3%)

487 (25.9%)

153 (8.1%)

1882≥ 30.06 (1.7%)207 (59.3%)

110 (31.5%)

26 (7.4%)349

Pre-existing condition at wave 1
Hypertension

34 (1.6%)

1577 (74.8%)402 (19.1%)

96 (4.6%)

2109

Dyslipidemia

25 (2.1%)

910 (76.2%)

200 (16.8%)

59 (4.9%)

1194

Diabetes

9 (1.4%)482 (72.5%)

136 (20.5%)

38 (5.7%)

665

Heart disease

7 (2.2%)234 (74.3%)

56 (17.8%)

18 (5.7%)315

Renal disease

2 (2.1%)66 (68.8%)

23 (24.0%)

5 (5.2%)

96

Cancer4 (2.0%)146 (73.7%)

36 (18.2%)

12 (6.1%)

198

Respiratory disease

5 (1.8%)180 (65.2%)

66 (23.9%)

25 (9.1%)

276

Other

2 (1.2%)102 (60.0%)50 (29.4%)

16 (9.4%)

170

Generalized trust at wave 1
Most people can be trusted

70 (1.8%)2604 (67.9%)

929 (24.2%)

234 (6.1%)

3837

Need to be very careful

132 (1.8%)4220 (56.4%)

2369 (31.7%)760 (10.2%)

7481

Don’t know

7 (1.3%)262 (49.6%)

200 (37.9%)

59 (11.2%)

528

Generalized trust at wave 3
Most people can be trusted

63 (1.7%)

2532 (69.5%)

822 (22.6%)

225 (6.2%)

3642

Need to be very careful

139 (1.8%)4287 (55.9%)2473 (32.3%)

765 (10.0%)

7664

Don’t know

7 (1.3%)267 (49.4%)

203 (37.6%)

63 (11.7%)

540

Depression (PHQ-9) at wave 1
None (0–4)

113 (1.5%)4761 (65.1%)

1899 (26.0%)

540 (7.4%)

7313

Mild (5–9)

56 (2.0%)1533 (54.2%)

949 (33.6%)

290 (10.3%)2828

Moderate (10–14)

24 (2.4%)

497 (49.2%)

375 (37.1%)

115 (11.4%)

1011

Moderately severe (15–19)

12 (2.5%)

209 (44.0%)

183 (38.5%)

71 (14.9%)

475

Severe (20–27)

4 (1.8%)86 (39.3%)

92 (42.0%)

37 (16.9%)

219

Depression (PHQ-9) at wave 3
None (0–4)

110 (1.5%)4784 (65.0%)

1918 (26.1%)

545 (7.4%)

7357

Mild (5–9)

51 (1.9%)

1511 (55.2%)

919 (33.6%)

257 (9.4%)

2738

Moderate (10–14)

29 (2.9%)487 (48.7%)352 (35.2%)

131 (13.1%)

999

Moderately severe (15–19)

10 (2.1%)

209 (43.1%)

192 (39.6%)

74 (15.3%)

485

Severe (20–27)

9 (3.4%)95 (35.6%)

117 (43.8%)

46 (17.2%)

267

140 (1.6%)

5628 (63.0%)2453 (27.5%)

714 (8.0%)8935

Generalized anxiety (GAD-7) at wave 1
Minimal (0–4)

Sekizawa et al. BMC Public Health(2022) 22:126

Page 7 of 17

Table 1 (continued)
Predictors

Already vaccinatedNot vaccinatedWilling

Total
Undecided

Unwilling

Mild (5–9)

38 (2.0%)998 (52.8%)662 (35.0%)

192 (10.2%)

1890

Moderate (10–14)

23 (3.3%)

321 (46.0%)

260 (37.2%)

94 (13.5%)

698

Severe (15–21)

8 (2.5%)139 (43.0%)

123 (38.1%)

53 (16.4%)

323

Generalized anxiety (GAD-7) at wave 3
Minimal (0–4)

133 (1.5%)

5588 (63.3%)

2412 (27.3%)

690 (7.8%)8823

Mild (5–9)

43 (2.2%)

1032 (52.5%)

694 (35.3%)

197 (10.0%)

1966

Moderate (10–14)

22 (3.4%)306 (47.1%)

226 (34.8%)

96 (14.8%)

650

Severe (15–21)

11 (2.7%)

160 (39.3%)

166 (40.8%)70 (17.2%)

407

Fear of COVID-19 (FCV-19S) at wave 1
No fear (7–15)

65 (1.8%)2066 (56.7%)

1056 (29.0%)456 (12.5%)

3643

Mild (16–20)

79 (1.9%)2556 (62.8%)

1152 (28.3%)

285 (7.0%)4072

Moderate (21–25)

45 (1.5%)

1761 (59.5%)

934 (31.6%)

218 (7.4%)

2958

Severe (26–35)

20 (1.7%)703 (59.9%)356 (30.3%)

94 (8.0%)

1173

Fear of COVID-19 (FCV-19S) At wave 3
No fear (7–15)

55 (1.8%)

1686 (54.7%)

869 (28.2%)

472 (15.3%)

3082

Mild (16–20)

72 (1.8%)2514 (62.7%)

1159 (28.9%)262 (6.5%)

4007

Moderate (21–25)

56 (1.7%)

1992 (60.1%)

1041 (31.4%)

228 (6.9%)

3317

Severe (26–35)

26 (1.8%)894 (62.1%)

429 (29.8%)

91 (6.3%)

1440

Region of residence at wave 1
Tokyo

21 (1.7%)

718 (57.9%)368 (29.7%)

133 (10.7%)

1240

Kanagawa

9 (1.0%)528 (61.5%)

266 (31.0%)

56 (6.5%)

859

Osaka

10 (1.2%)

520 (61.3%)

240 (28.3%)

78 (9.2%)

848

Aichi

10 (1.4%)

449 (61.8%)203 (28.0%)

64 (8.8%)

726

Saitama

9 (1.3%)413 (59.8%)

220 (31.8%)

49 (7.1%)

691

Chiba

8 (1.3%)374 (60.9%)

165 (26.9%)

67 (10.9%)

614

Hyogo

3 (0.5%)341 (62.1%)

153 (27.9%)

52 (9.5%)

549

Hokkaido

7 (1.3%)328 (61.9%)

146 (27.5%)

49 (9.2%)

530

Fukuoka

5 (1.1%)259 (59.3%)

120 (27.5%)

53 (12.1%)

437

Tohoku region

14 (1.7%)509 (63.1%)

220 (27.3%)

64 (7.9%)807

North Kanto

14 (2.3%)

341 (56.7%)

195 (32.4%)

51 (8.5%)

601

Hokuriku

9 (1.9%)280 (60.6%)

138 (29.9%)35 (7.6%)

462

Chubu

16 (1.9%)492 (59.3%)

260 (31.4%)

61 (7.4%)

829

Kinki

15 (1.8%)513 (60.1%)

240 (28.1%)

85 (10.0%)853

Chugoku

19 (2.8%)384 (55.8%)230 (33.4%)

55 (8.0%)

688

Shikoku

12 (3.5%)

214 (62.4%)

87 (25.4%)

30 (8.7%)

343

Kyushu and Okinawa

28 (3.6%)423 (55.0%)

247 (32.1%)

71 (9.2%)769

moderate depression lost significance in Model 2 at wave
3. With regard to unwillingness, Model 1 at wave 1 andwave 3 showed that those who were mildly depressed(at wave 1 only), moderately depressed (at wave 3 only),
moderate-severely depressed, and severely depressed
were more likely to be unwilling to be vaccinated thanthose who were not depressed. In Model 2 at wave 1
and wave 3, in which generalized trust, generalized
anxiety, and fear of COVID-19 were adjusted for, there
were no significant associations between depression

and unwillingness to be vaccinated except that mild
depression at wave 1 and moderate depression at wave 3
remained significant.
Regarding generalized anxiety, Model 1 at wave 1
and wave 3 showed that those who were mildly anxious
and severely anxious (at wave 3 only) were more likely
to be undecided about whether to receive a vaccine
than respondents who had minimal levels of anxiety.
In Model 2 at wave 1 and wave 3, in which generalized
trust, depression, and fear of COVID-19 were adjusted

0.0181.48(0.69–0.95)

0.81  Minimal (0–4)

Generalized anxiety (GAD-7)

reference(1.19–2.17)(1.21–2.79)

1.61

1.84

   Moderately severe (15–19)  Severe (20–27)

0.002
0.004

reference

1.97(1.34–2.89)(1.36–2.47)

1.50(0.93–1.50)

1.18  Moderate (10–14)< 0.001< 0.001< 0.0010.307< 0.001< 0.001

0.007

0.466

0.043

< 0.001

0.181

0.005

< 0.001< 0.001

0.020

0.010

< 0.001< 0.001

P-Valuereferencereference

1.53

1.48

1.19

1.30

reference

1.90

1.59

reference

0.74

0.90

0.86

reference

0.86

0.96

1.00

reference

1.63

1.38

1.22

1.19

reference

1.65

1.28

(0.87–2.71)(0.99–2.22)(0.89–1.59)(1.08–1.55)(1.37–2.63)(1.35–1.87)(0.62–0.87)(0.80–1.02)(0.77–0.96)(0.60–1.23)(0.75–1.21)(0.87–1.16)(1.08–2.47)(1.04–1.82)(1.01–1.47)(1.06–1.34)(1.34–2.04)(1.16–1.41)

95% CI

Model 2 at wave 1
RRR​

0.140

0.055

0.253

0.005

< 0.001< 0.001< 0.001

0.094

0.006

0.402

0.706

0.965

0.020

0.025

0.043

0.003

< 0.001< 0.001

P-Valuereference(1.32–1.61)

reference

1.29

1.44

1.41

1.14

reference

1.95

1.63

reference

0.70(0.74–2.25)(0.96–2.16)(1.06–1.88)(0.94–1.38)(1.41–2.70)(1.38–1.93)(0.59–0.82)(0.76–0.96)(0.78–1.00)

0.88(0.77–1.55)(0.74–1.20)(0.94–1.24)(1.07–2.40)(1.11–1.93)(0.96–1.40)(0.98–1.24)(1.42–2.16)

0.86

reference

1.10

0.94

1.08

reference

1.60

1.46

1.16

1.10

reference

1.75

1.45

95% CI

Model 2 at wave 3
RRR​

0.376

0.074

0.020

0.191

< 0.001< 0.001< 0.001

0.046

0.009

0.606

0.629

0.291

0.022

0.007

0.133

0.113

< 0.001< 0.001

P-Value(2022) 22:126

1.83(1.20–1.88)

1.09

0.162

(0.92–1.29)

reference
0.005

1.26
(1.07–1.48)

reference  Mild (5–9)(1.28–2.43)(1.34–1.86)(0.70–0.95)(0.85–1.08)(0.79–1.00)  None (0–4)

Depression (PHQ-9)(1.33–2.54)

1.84  Don’t know

1.76

1.58

1.58
< 0.001reference((1.34–1.85)

reference

0.81   Need to be very careful< 0.001

0.008   Most people can be trusted

Generalized trust

Unwilling to vaccinate at wave 3  Severe (26–35)(0.85–1.08)

0.96  Moderate (21–25)

0.96

0.89

0.88
0.482

referencereference(1.20–1.91)  Mild (16–20)

0.020

0.243

   No fear (7–15)(0.79–0.98)(0.90–1.51)

1.51

1.17

Fear of COVID-19 (FCV-19S)  Severe (15–21)(0.94–1.37)(1.05–1.32)(1.26–2.25)(1.19–1.83)(1.03–1.40)(1.03–1.27)(1.44–2.20)(1.34–1.63)

1.14

1.16

  Moderate (10–14)

0.101

1.18

1.13
(0.97–1.39)

referencereference

1.69  Mild (5–9)

0.045

0.017

  Minimal (0–4)(1.00–1.27)(1.05–1.62)(1.07–2.00)

1.30

1.46

   Moderately severe (15–19)  Severe (20–27)

Generalized anxiety (GAD-7)(1.02–1.39)

1.20  Moderate (10–14)

1.20

1.15

0.024

reference

1.19  Mild (5–9)< 0.001(1.07–1.32)

reference  None (0–4)

Depression (PHQ-9)(1.36–2.08)

1.68  Don’t know

1.78

1.48

< 0.001reference

1.29< 0.001(1.17–1.42)

reference   Need to be very careful

95% CI

Model 1 at wave 3
P-Value

RRR​

95% CI

Model 1 at wave 1

RRR​   Most people can be trusted

Generalized trust

Undecided on vaccination at wave 3

Dependent variable

Table 2 Results of the adjusted multinomial logistic regression analyses

Sekizawa et al. BMC Public HealthPage 8 of 17

(1.09–2.17)

1.54(0.43–0.62)(0.39–0.64)

0.52

0.50

  Moderate (21–25)  Severe (26–35)

0.32(0.96–1.37)(0.25–0.41)(0.32–0.46)(0.31–0.44)(1.48–2.75)(1.21–2.02)< 0.001< 0.001< 0.001< 0.001< 0.001

0.132

P-Value

0.41

0.47

0.50

reference

1.28

1.24

1.03

RRR​

(0.31–0.53)(0.39–0.56)(0.42–0.59)(0.78–2.10)(0.88–1.75)(0.83–1.29)

95% CI

Model 2 at wave 1< 0.001< 0.001< 0.001

0.331

0.228

0.765

P-Value

0.22

0.33

0.35

reference

2.01

1.56

1.18

RRR​

(0.17–0.29)(0.27–0.39)(0.29–0.42)(1.24–3.25)(1.10–2.21)(0.95–1.48)

95% CI

Model 2 at wave 3< 0.001< 0.001< 0.001

0.005

0.014

0.141

P-Value

RRR​Relative Risk Ratio, CI Confidence Interval, PHQ-9 Patient Health Questionnaire-9, GAD-7 Generalized Anxiety Disorder-7, FCV-19S Fear of COVID-19 Scale

Boldface indicates statistical significance at the 5% level (both sides). Estimates are RRRs derived from multinomial logistic regression analyses. Model 1 adjusted for any one of generalized trust, PHQ-9, GAD-7, andFCV-19S, plus other explanatory variables (sex, age group, level of education, family members living together, employment, annual household income, bank and saving deposit amount, BMI, pre-existing conditions,and region of residence). Model 2 adjusted for all of generalized trust, PHQ-9, GAD-7, and FCV-19S together, plus other explanatory variables. For all analyses, willingness to be vaccinated at wave 3 was the outcome
reference group. Generalized trust, PHQ-9, GAD-7, FCV-19S, age group, employment, annual household income, and bank and saving deposit amount in Model 1 and 2 at wave 1 and wave 3 were those at wave 1 and 3,
respectively. Remaining explanatory variables were those at wave 1< 0.001

0.38

0.37

0.52
< 0.001reference(0.44–0.61)

reference

2.02  Mild (16–20)< 0.001

0.014

1.15
1.56

   No fear (7–15)

Fear of COVID-19 (FCV-19S)  Severe (15–21)

0.019

0.433

(0.90–1.29)(1.05–1.76)

1.08

1.36

  Mild (5–9)

95% CI

RRR​

P-Value

RRR​

95% CI

Model 1 at wave 3

Model 1 at wave 1  Moderate (10–14)

Dependent variable

Table 2 (continued)

Sekizawa et al. BMC Public Health(2022) 22:126
Page 9 of 17

Sekizawa et al. BMC Public Health(2022) 22:126

for, there were no significant associations between generalized anxiety and indecisiveness regarding vaccination. With regard to unwillingness, Model 1 at wave 1
and wave 3 showed that those who were moderately anxious and severely anxious were more likely to be unwilling to be vaccinated than those who had a minimal levelof anxiety. In Model 2 at wave 1 and wave 3, in which
generalized trust, depression, and fear of COVID-19
were adjusted for, moderate anxiety and severe anxiety
at wave 1 lost significance, but those at wave 3 remained
significant.
Regarding fear of COVID-19, Model 1 at wave 1 andwave 3 showed that participants with mild and severe fearof COVID-19 were less likely to be undecided regarding
vaccination than those who had no fear of COVID-19. In
Model 2 at wave 1 and wave 3, in which generalized trust,depression, and generalized anxiety were adjusted for,the results were basically the same except that moderate fear of COVID-19 at wave 3 gained significance. With
regard to unwillingness, Model 1 at wave 1 and at wave 3
showed that respondents with mild, moderate, and severe
fear of COVID-19 were less likely to be unwilling to be
vaccinated than those who had no fear of COVID-19. In
Model 2 at wave 1 and wave 3, in which generalized trust,depression, and fear of COVID-19 were adjusted for, theresults remained basically the same.
Association of other explanatory variables with attitudes
toward vaccination against COVID‑19

The results of Model 2 at wave 1, in which all explanatory variables were included, are shown in Table 3. Being
female (undecided only), having a lower level of education, low household income, low savings, and low BMI
were positively associated with indecisiveness or unwillingness. Older age, living only with a spouse, and having
hypertension or dyslipidemia were negatively associated with indecisiveness and unwillingness. The resultsof Model 2 at wave 3 were basically the same (shown in
Supplementary Table 1).

Discussion
In the present study, we explored whether generalized
trust, mental health factors such as depression and generalized anxiety, and fear of COVID-19 are predictors ofvaccine hesitancy against COVID-19. We used the dataon wave 1 (between October 27 and November 6, 2020)
and wave 3 (between April 23 and May 6, 2021) of a longitudinal online survey carried out in Japan. We found
that: (1) respondents who had lower levels of generalized
trust at wave 1 and 3 were more likely to be undecided
or unwilling to be vaccinated at wave 3; (2) respondents
with moderately severe or severe levels of depression at
wave 1 and 3 were more likely to be undecided about

Page 10 of 17

being vaccinated at wave 3; (3) respondents with moderate or severe levels of generalized anxiety at wave 3 but
not at wave 1 were more likely to be unwilling to be vaccinated at wave 3; and (4) participants with high levelsof fear of COVID-19 at wave 1 and 3 were less likely to
be undecided or unwilling to be vaccinated at wave 3.
In addition to these results, our findings confirmed theresults of previous studies that found that younger people, women, people with low incomes, and people withlower levels of education were more likely to be undecided or unwilling to be vaccinated.
The wave 3 survey, in which the question on vaccine
hesitancy was asked, was conducted between April 23
and May 6, 2021, in Japan, where vaccination against
COVID-19 for medical personnel began on February
17, 2021, a few months later than Europe and the UnitedStates. On April 12, vaccination for persons aged 65 andover was initiated. As of April 23, the shares of the Japanese populations that had received at least one dose of
the COVID-19 vaccine and been fully vaccinated against
COVID-19 were 1.7 and 0.7%, respectively [1]. As of
April 23, total cases of COVID-19 per million people
were 4426 and total deaths per million people were 78 in
Japan [1]. Hence, the ratios of those who were vaccinatedagainst COVID-19 and casualties due to COVID-19 werelower in Japan than in many other countries. The declaration of a state of emergency was in effect in several areasof Japan including Tokyo and Osaka at that time in order
to inhibit the spread of COVID-19. The results of the present study must be interpreted against this background.
Regarding generalized trust in people, the present
study showed that participants with low levels of generalized trust at waves 1 and 3 were more likely to be undecided or unwilling to be vaccinated at wave 3. Wave 1 wasapproximately 6 months before wave 3. Therefore, thepresent study suggest that the level of generalized trust
predicts vaccine hesitancy 6 months later. This finding
is consistent with the two previous studies that reported
that those who indicated a higher level of generalized
trust tended to be more willing to get a COVID-19 vaccine than those with a lower level of generalized trust [31,36]. The relationship between generalized trust and vaccine hesitancy in general was addressed in a systematic
review by Larson et al. [25]. However, only three of thereviewed studies examined the relationship between generalized trust and vaccination, and one of them examined
trust in the government. Two studies [37, 39] referred toin Larson et al. and another study [38] reported findings
consistent with the present study; that is, participants
with high generalized trust were more willing to be vaccinated against influenza. Hence, studies thus far, including
the present one, have consistently shown that generalized
trust is positively associated with vaccine acceptance.

Sekizawa et al. BMC Public Health(2022) 22:126

Page 11 of 17

Table 3 Results of the fully adjusted multinomial logistic regression analyses at wave 1
Predictors

Undecided
RRR​

Unwilling
95% CI

P-value

RRR​(1.07–1.32)

0.001

1.13

95% CI

P-value(0.96–1.32)

0.145

Sex
Male

reference

Female1.19

reference

Age group, years
65+

reference

50–64

2.35

(2.04–2.70)< 0.001

1.82

reference(1.44–2.29)< 0.001

30–49

3.58

(3.06–4.19)< 0.001

3.04(2.35–3.91)< 0.001

18–29

4.16

(3.35–5.16)< 0.001

4.46(3.23–6.15)< 0.001

Highest education
Junior/senior high school

1.21(1.09–1.35)< 0.001

1.32(1.11–1.56)

0.001

Two- or three-year college

1.08(0.96–1.22)

0.185

1.28

(1.06–1.54)

0.009

Four-year college or higher

reference(1.16–1.84)

0.001

reference

Family members living together
Living alone

1.33

Living only with spouses

reference(1.15–1.54)< 0.001

1.46
reference

Living with children

1.15(1.02–1.29)

0.027

1.20

(0.98–1.47)

0.082

Living with parents

1.34(1.16–1.55)< 0.001

1.46(1.16–1.84)

0.001

Three generation household
Others (siblings only, friends, grandparents and grandchildren etc.)

1.49(1.21–1.83)< 0.001

1.40(0.99–1.98)

0.059

1.38

(0.97–1.96)

0.077

1.88

(1.17–3.00)

0.009

Employment
Employedreference

Homemaker

1.09(0.95–1.25)

0.208

0.86

reference(0.68–1.08)

0.198

Not employed (seeking a job)

0.98

(0.74–1.28)

0.858

0.98

(0.67–1.45)

0.937

Not employed (not seeking job)

1.06

(0.91–1.24)

0.437

1.29

(1.03–1.61)

0.026

Student

0.88(0.64–1.21)

0.420

0.72

(0.46–1.11)

0.137

Other

1.60

(1.05–2.42)

0.028

1.99

(1.14–3.47)

0.015Annual household income, million yen
<3

1.35

(1.15–1.58)< 0.001

1.39(1.09–1.77)

0.008

3–4

0.99

(0.86–1.14)

0.871

0.96

(0.77–1.20)

0.730

5–7

1.12

(0.98–1.28)

0.086

0.87

(0.70–1.08)

0.216

≥8

referencereference

Bank and saving deposit amount, million yen
<1

1.44

(1.27–1.64)< 0.001

1.45(1.18–1.77)< 0.001

1–3

1.23(1.08–1.40)

0.002

1.13

(0.92–1.40)

0.242

4–9

1.23

(1.08–1.39)

0.001

1.13

(0.92–1.39)

0.238

≥ 10

reference(1.10–1.62)

0.003

reference

BMI< 18.5

1.17

18.5–24.9

reference(1.03–1.34)

0.019

1.34
reference

25.0-29.9

0.94(0.83–1.07)

0.341

1.02

(0.84–1.25)

0.827≥ 30.00.97(0.75–1.26)

0.833

0.76

(0.49–1.19)

0.232

Pre-existing condition
Hypertension

0.79(0.69–0.90)< 0.001

0.62(0.49–0.78)< 0.001

Dyslipidemia

0.62(0.52–0.73)< 0.001

0.68(0.51–0.91)

0.009

Diabetes

0.95(0.77–1.17)

0.610

0.88

(0.62–1.27)

0.501Heart disease

0.86(0.63–1.17)

0.338

0.94

(0.56–1.56)

0.802

Renal disease

1.12(0.67–1.85)

0.674

0.70

(0.27–1.81)

0.467

Sekizawa et al. BMC Public Health(2022) 22:126

Page 12 of 17

Table 3 (continued)
Predictors

Undecided
RRR​

Unwilling
95% CI

P-value

RRR​

95% CI

P-value

Cancer0.74(0.50–1.09)

0.126

0.82

(0.44–1.52)

0.522

Respiratory disease

0.97(0.71–1.31)

0.838

1.23

(0.78–1.92)

0.369

Other condition

1.03(0.71–1.47)

0.890

1.02

(0.58–1.77)

0.952

Region of residenceTokyo

reference

Kanagawa

1.05(0.85–1.29)

0.652

0.64

reference(0.45–0.90)

0.011

Osaka

0.93

(0.75–1.14)

0.479

0.83

(0.60–1.13)

0.237

Aichi

0.90

(0.72–1.12)

0.343

0.80

(0.57–1.11)

0.180

Saitama

1.12(0.90–1.39)

0.319

0.69

(0.48–1.00)

0.049

Chiba

0.93

(0.73–1.17)

0.525

1.05

(0.75–1.47)

0.776

Hyogo

0.92

(0.72–1.17)

0.496

0.87

(0.61–1.25)

0.457

Hokkaido

0.86(0.67–1.10)

0.225

0.80

(0.55–1.15)

0.227

Fukuoka

0.84(0.64–1.09)

0.187

1.01

(0.70–1.46)

0.964

Tohoku region

0.74(0.59–0.91)

0.005

0.61

(0.44–0.86)

0.004

North Kanto

1.15(0.92–1.45)

0.228

0.84

(0.59–1.22)

0.365

Hokuriku

0.92(0.71–1.18)

0.501

0.64

(0.42–0.97)

0.037

Chubu

1.06

(0.86–1.30)

0.593

0.67

(0.47–0.93)

0.019

Kinki

0.96

(0.78–1.19)

0.713

0.96

(0.71–1.31)

0.817

Chugoku

1.30(1.05–1.63)

0.018

0.89

(0.63–1.27)

0.535

Shikoku

0.81(0.60–1.09)

0.156

0.81

(0.52–1.27)

0.358

Kyushu and Okinawa

1.10(0.89–1.36)

0.389

0.86

(0.61–1.19)

0.354

Generalized trust
Most people can be trusted

reference

Need to be very careful

1.28(1.16–1.41)< 0.001

1.59

reference(1.35–1.87)< 0.001

Don’t know

1.65

(1.34–2.04)< 0.001

1.90(1.37–2.63)< 0.001

Depression (PHQ-9)
None (0–4)

reference

Mild (5–9)

1.19(1.06–1.34)

0.003

1.30

reference(1.08–1.55)

0.005

Moderate (10–14)

1.22(1.01–1.47)

0.043

1.19

(0.89–1.59)

0.253

Moderately severe (15–-19)

1.38(1.04–1.82)

0.025

1.48

(0.99–2.22)

0.055

Severe (20–27)

1.63(1.08–2.47)

0.020

1.53

(0.87–2.71)

0.140

Generalized anxiety (GAD-7)
Minimal (0–4)

reference

Mild (5–9)

1.00(0.87–1.16)

0.965

1.03

reference(0.83–1.29)

0.765

Moderate (10–14)

0.96(0.75–1.21)

0.706

1.24

(0.88–1.75)

0.228

Severe (15–21)

0.86(0.60–1.23)

0.402

1.28

(0.78–2.10)

0.331

Fear of COVID-19 (FCV-19S)
No fear (7–15)

reference

Mild (16–20)

0.86(0.77–0.96)

0.006

0.50

reference(0.42–0.59)< 0.001

Moderate (21–25)

0.90(0.80–1.02)

0.094

0.47

(0.39–0.56)< 0.001

Severe (26–35)

0.74(0.62–0.87)< 0.001

0.41(0.31–0.53)< 0.001

Boldface indicates statistical significance at the 5% level (both sides). Estimates are RRRs derived from multinomial logistic regression analyses adjusting for all ofgeneralized trust, PHQ-9, GAD-7, and FCV-19S, plus other explanatory variables (sex, age group, level of education, family members living together, employment,
annual household income, bank and saving deposit amount, BMI, pre-existing conditions, and region of residence). All explanatory variables are those at wave 1.
Willingness to be vaccinated at wave 3 was the outcome reference group
RRR​Relative Risk Ratio, CI Confidence Interval, PHQ-9 Patient Health Questionnaire-9, GAD-7 Generalized Anxiety Disorder −7, FCV-19S Fear of COVID-19 ScaleSekizawa et al. BMC Public Health(2022) 22:126

How generalized trust is related to vaccine acceptancenot only with regard to COVID 19, but also other diseases, has not been sufficiently explored. Although we did
not examine the mechanisms linking generalized trustand vaccine acceptance in the present study, previous
studies suggest two possible explanations. First, individuals with high levels of generalized trust tend to be morealtruistic and intend to contribute to the public healthpolicy of containing COVID-19 [37]. Another possible
explanation is that individuals with lower levels of generalized trust may have distrust related to a wide range ofissues, including the performance of government [65, 66],
the safety of the vaccine, and even medical treatments ingeneral [31], leading to vaccine hesitancy. The association
between vaccine acceptance and various forms of specifictrust, including trust in vaccines, trust in the government, trust in the health system, or in professionals, hasalready been shown in COVID-19 vaccination [6, 16, 20,
22, 26–33] and in general [24, 25]. Several studies, mainlyin the social sciences, have demonstrated the positive
association between generalized trust and some types of
specific trust [65, 66]. However, to our knowledge, themediating role of specific trust between generalized trustand vaccine hesitancy has only been explored in Ahorsu
et al. [31]. Further studies are recommended to explore
how lower levels of generalized trust are associated with
COVID-19 vaccine hesitancy.
Regarding the relationship between depression/anxiety and attitudes toward vaccination, the present study
showed that participants with depression at waves 1 and3 were more likely to be undecided regarding vaccination
at wave 3, and participants with generalized anxiety atwave 3 but not at wave 1 were more likely to be unwilling to be vaccinated at wave 3. There are two things to
be considered regarding this finding based on previous
studies dealing with similar topics. First, studies in the
United States, China, and Germany [15, 17, 41] found no
significant association between depression/anxiety andattitudes toward COVID-19 vaccination, whereas thepresent study as well as some previous studies [22, 42]
found a positive association between psychological distress and vaccine hesitancy. The reason for this disparity
is unclear but might be due to the large sample size of ourstudy, which enabled the identification of even minor differences. Another thing to be considered is that studies
that address the relationship between depression/anxiety
and attitudes toward vaccination other than COVID-19[43–45] seem to have contradictory results compared tothe present study and the two above-mentioned studies
on COVID-19 [22, 42], despite the fact that the themes
these studies addressed are mostly the same. Chan et al.
[43] showed that those who were more anxious weremore willing to receive vaccination against A/H7N9

Page 13 of 17

influenza in Hong Kong. Lawrence et al. [44] reported
that older primary care patients with mental health diagnoses were more likely to receive vaccination against
influenza although the outcome in this study was realvaccine uptake instead of willingness to receive vaccination. Similarly, Mohammed et al. [45] reported that pregnant women with mild depression/anxiety were more
likely to receive influenza vaccination during pregnancy
although there was no association between depression/anxiety and willingness to receive vaccination.
Questions still remain as to how mental health factors
such as depression and anxiety are associated with vaccine hesitancy in some studies regarding COVID-19, andwhy the studies on influenza seem to have contradictory
results. In addressing these questions, the differences
between depression and anxiety may need to be considered. One characteristic of people with depression isthat they tend to have difficulty making decisions [67].
The present study’s finding that people with depression
tend to be undecided about COVID-19 vaccination may
be explained by this general indecisiveness. People withgeneralized anxiety are generally risk averse [68], butwhat they are anxious about is not predetermined. In
the case of vaccination, while there are risks such as side
effects from the vaccine, there is also an increased risk of
becoming infected with COVID-19 and severely ill by notgetting vaccinated. Hence, which of these two risks people with generalized anxiety will prioritize is difficult todetermine beforehand without data analysis. The resultsof the present study suggest that those with moderate andsevere level of generalized anxiety at the moment tend toprioritize avoiding the risks associated with getting vaccinated against COVID-19 rather than being infectedwith COVID-19. Contrastingly, the results of the previous studies [43–45] suggest that those with moderate andsevere levels of generalized anxiety tend to prioritize theavoidance of the risks associated with infection (mainly
for influenza) over the risks associated with the vaccine.
Although we do not have clear answers to explain thisseeming difference, there are several possible explanations. First, the subjects in Lawrence et al. [44] were older
primary care patients and the subjects in Mohammed
et al. [45] were pregnant women who attended an antenatal clinic. By contrast, the subjects in the present study
were mostly members of the general public and did notbelong in a clinical setting. This difference may explain
the variation in results. Second, Chan et al. [43] demonstrated a positive association between anxiety level andwillingness to be vaccinated for A/H7N9 influenza basedon a population telephone survey, whereas the present
study examined the willingness to receive vaccination
against COVID-19 based on an online survey. Such differences may explain the seemingly contradictory results.

Sekizawa et al. BMC Public Health(2022) 22:126

Overall, studies exploring the relationship between
depression/anxiety and vaccine hesitancy have shownvaried results. The diseases that the vaccines are meant
to prevent (e.g., COVID-19, seasonal influenza), themethods of measurement of depression/anxiety (e.g.,
self-administered questionnaire, diagnoses at clinical settings), the coverage of study subjects (e.g., elderly people, pregnant women, general population), as well as thedifferences in cultural and political backgrounds may be
responsible for the varied results in different studies. Further studies are recommended, considering the resultsof previous studies that are inconsistent with the present
study [15, 17, 41, 43–45] and actual vaccination behaviors
rather than willingness to receive a vaccine.
The present study found that people with high levelsof fear of COVID-19 at waves 1 and 3 were more likely
to be willing to receive a vaccine at wave 3. This finding
is consistent with most studies that addressed this issue[15, 22, 26, 27, 41, 46–48, 54]. A typical characteristic offear is that people tend to avoid what they fear. Hence,
the most plausible explanation of the negative association
between the fear of COVID-19 and vaccine hesitancy isthat people with high levels of fear of COVID-19 try to
avoid what they fear, namely COVID-19, by getting vaccinated against it. In contrast to most studies including thepresent one, an older study carried out in Lebanon [46]found no significant association between the willingness
to receive the COVID-19 vaccine and the fear of COVID19. The reasons for the difference might be cultural or adifference in sample size.
According to the present study, younger people,
women, people with low incomes, and people with lower
levels of education are more likely to be undecided or
unwilling to be vaccinated. These results are consistent
with many previous studies that claim that younger people [6, 7, 11, 13–15, 18–22], women [6, 7, 9–12, 14–16,
19–23], people with low incomes [6, 11, 13–15, 18, 19,
21, 22], and people with lower levels of education [6, 7,
10, 13–16, 20, 22, 23] were reluctant to receive a vaccine.
Vaccine hesitancy due to younger age and being female
may be due to decreased anxiety compared to older
males, as there is widely shared information that older
people and men are more likely to be seriously affectedby COVID-19 infection [69, 70]. Regarding socioeconomic status derived mainly based on income and education, a plausible mediator between low socioeconomic
status and vaccine hesitancy is low levels of health protective behaviors due to poor health literacy in people
with low socioeconomic status [71–73]. A mediatingrole of health literacy between socioeconomic status and
COVID-19 vaccination hesitancy is suggested in a previous article [72], although it is unclear whether health literacy is the only mediator between them [74]. Therefore,

Page 14 of 17

it is safe to state that mechanisms linking such sociodemographic variables and vaccine hesitancy have not been
sufficiently explored so far, and further investigation isrecommended.
The following limitations must be kept in mind when
considering the results of the present study. First, theparticipants in the present study were not representativeof the general population. The present study was basedon wave 1 and wave 3 of a longitudinal online survey withthe respondents limited to those who responded bothat wave 1 and wave 3. Although wave 1 was designed
to reflect sex, age, and place of residence at the prefecture level of the entire Japanese population, there was
no random sampling in the extraction of the survey participants. In addition, the number of valid respondents
at wave 3 was approximately 70% of wave 1. Moreover,the present study was an Internet-based survey; participants were required to have access to the Internet.
Possibly reflecting this requirement, almost half of ourparticipants had attended four-year colleges, a percentage
greater than Japan’s national average. Second, potentially
important confounders may not have been adjusted forin the present study. We asked only one question on generalized trust. Specific trusts not covered by the present
study may be confounders. Other potential confounders
such as place of residence (rural vs urban area) were notincorporated in the present study due to the data constraints. Hence, there remains a possibility that associations between generalized trust (or depression/anxiety,fear of COVID-19) and vaccine hesitancy might be spurious. Third, unlike in many other studies on vaccine hesitancy, COVID-19 vaccination had already started whenthe question on vaccination was being asked (wave 3),although less than 2% of Japanese people had been vaccinated by wave 3. This may have had some impact on
attitudes toward vaccine hesitancy. Finally, the present
study was an observational study and, thus, cannot demonstrate a causal relationship between the explanatory
variables and the outcome variables.

Conclusions
The present study explored the associations between
unwillingness and indecisiveness regarding being vaccinated against COVID-19 with generalized trust,depression, and generalized anxiety. In our findings, low
generalized trust, depression, and generalized anxiety
were associated with unwillingness and indecisiveness to
be vaccinated against COVID-19. In order to determine
whether such associations are observed in other countries with different cultures, further epidemiological or
sociological studies using global data may be needed.

Sekizawa et al. BMC Public Health(2022) 22:126

Page 15 of 17

Abbreviations
BMI: Body mass index; COVID-19: Coronavirus disease of 2019; FCV-19S: Fear of
COVID-19 Scale; GAD-7: Generalized Anxiety Disorder-7; PHQ-9: Patient Health
Questionnaire-9; RIETI: Research Institute of Economy, Trade and Industry; RRR​:
Relative risk ratio; WVS: World Values Survey.

2.

Supplementary Information

4.

The online version contains supplementary material available at https://​doi.​
org/​10.​1186/​s12889-​021-​12479-w.
Additional file 1: Supplementary Table 1. Results of the Fully Adjusted
Multinomial Logistic Regression Analyses at wave 3.
Acknowledgements
We would like to thank the participants.
Authors’ contributions
YS, SH, KD, SO, and SM designed the study; YS drafted the manuscript, carriedout the analysis, and interpreted the results; SH and SO assisted in drafting andreviewing the manuscript; All authors reviewed the final manuscript and gave
their consent.
Funding
The present study was funded by the RIETI, Japan. The RIETI was involved in
the conduct of the study through its contract with NTTCom Online Marketing
Solutions Corporation. The RIETI had no role in the study design, data analyses,
decision to publish, or preparation of the manuscript.
Availability of data and materials
The data used in the present study belong to the RIETI and can be obtained
from the institute upon reasonable request.

Declarations
Ethics approval and consent to participate
Ethical approval was obtained from the ethics committee of Hiramatsu
Memorial Hospital (No: 20200925). All individuals who participated in thisstudy provided online informed consent for their participation. All methods
were carried out in accordance with relevant guidelines and regulations.

3.

5.
6.

7.

8.

9.

10.

11.

12.
13.

14.

Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.

15.

Author details
1
Research Institute of Economy, Trade and Industry, Chiyoda‑ku, Kasumigaseki 1‑3‑1, Tokyo 100‑8901, Japan. 2 United Health Communication Co., Ltd.,
Chuo‑ku, Nihonbashitomizawacho 10‑16, Tokyo 103‑0006, Japan. 3 Hiramatsu
Memorial Hospital, Chuo‑ku Minami 22‑jo nishi 14‑1‑20, Sapporo‑shi, Hokkaido 064‑8536, Japan. 4 Department of Laboratory Medicine, The Jikei University School of Medicine, Minato‑ku Nishishinbashi 3‑25‑8, Tokyo 105‑8461,
Japan. 5 Department of Psychiatry, Tokyo Dental College Ichikawa General
Hospital, Ichikawa‑shi, Sugano 5‑11‑13, Chiba 272‑8513, Japan.

16.

Received: 21 July 2021 Accepted: 22 December 2021

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