Skip to main content
PLOS One logoLink to PLOS One
. 2022 Dec 12;17(12):e0278967. doi: 10.1371/journal.pone.0278967

Factors associated with reluctancy to acquire COVID-19 vaccination: A cross-sectional study in Shiraz, Iran, 2022

Najmeh Maharlouei 1, Parisa Hosseinpour 2, Amirhossein Erfani 3,*, Reza Shahriarirad 3, Hadi Raeisi Shahrakie 1, Abbas Rezaianzadeh 4,5, Kamran Bagheri Lankarani 1
Editor: Srikanth Umakanthan6
PMCID: PMC9744289  PMID: 36508442

Abstract

Background

Vaccination is a crucial action that can end the COVID-19 pandemic and reduce its detrimental effect on public health. Despite the availability of various vaccines, this study was conducted to better understand the factors behind individuals refusing to get vaccinated.

Method

The current cross-sectional study was conducted with individuals above 18 years of age in Shiraz, Iran, who were eligible but refused to receive the COVID-19 vaccination. Demographic features and factors related to their hesitancy and willingness to participate in the vaccination program were recorded in a questionnaire.

Result

Out of 801 participants in the current study, 427 (53.3%) were men, with a mean age of 37.92 years (± 14.16). The findings revealed that 350 (43.7%) participants claimed the side effects of the vaccine outweigh the benefits as one reason for their reluctance toward COVID-19 vaccination, followed by the unknown efficacy of vaccines (40.4%) and a lack of trust in vaccine companies (32.8%). Ensuring the safety of the vaccine (43.7%) and verifying its effectiveness (34.5%) were the most prevalent factors behind participating in the vaccination program. Those who reported their socio-economic status as low were significantly reluctant toward vaccination because of a self-presumption of high immunity (p-value < 0.001), the unclear efficacy of vaccines (p-value < 0.001), the side effects outweighing the benefits of vaccines (p-value < 0.001), distrust of vaccine companies (p-value < 0.001), usage of mask, gloves, and sanitizers (p-value < 0.001), contradictory speech of health authorities regarding vaccines (p-value = 0.041), and the unavailability of trusted vaccines (p-value = 0.002). It should also be noted that participants reported a greater likelihood to obtain information about vaccination reluctance from family and friends (p-value <0.001) and complementary medicine professionals (p-value <0.001).

Conclusion

Avoiding vaccination is an undeniable public and individual health concern in Iran, as demonstrated in the current study. Concern about vaccine efficacy and side effects is the most reported cause of vaccination reluctance among individuals, which could be altered by emphasizing mass education and averting an infodemic by forming dedicated multidisciplinary organizations.

Introduction

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) [1, 2] was identified in Wuhan, China [3]. Despite attempts to contain the virus, the World Health Organization (WHO) soon declared a pandemic on the 11th of March 2020. Since then, more than 450 million people have contracted the disease and more than 6 million sufferers have died [4]. Alongside its effect on public health, the pandemic has triggered an enormous disruption in aspects of the economy and social life of people living in developing countries who are already dealing with difficulties, such as Iran [5, 6]. Thus, health authorities were obligated to take necessary actions to stop the spread of the virus to reduce its disturbing effects on public health.

Since the beginning of the pandemic, several tactics have been practiced to reduce the detrimental consequences of a pandemic, such as applying different available medicines [7], practicing lockdowns, social distancing, utilizing hand sanitizers, closure of public places, and travel restrictions [8]. Although these approaches helped flatten the pandemic curve, they were not the ultimate solution [9]. Vaccination is a crucial action to end the COVID-19 pandemic and reduce hospitalization and mortality [10]. However, the impact of vaccines on the pandemic also depends on several factors, such as the effectiveness of the vaccines, how quickly they are delivered, and how many people get vaccinated [10, 11]. Pfizer-BioNTech, Moderna’s mRNA-1273, and AstraZeneca/Oxford’s AZD1222 were among the first developed vaccines to obtain Food and Drug Administration (FDA) [12] approval for emergency use [13, 14]. Because of their remarkable effectiveness in reducing mortality and morbidity [15], the administration of these vaccines to most of the population was considered the only option for exiting the pandemic crisis. Although the percentage might differ among viruses due to the route of spread, the more people receive vaccination, the closer the population gets to herd immunity against COVID-19 [16].

While reaching a higher percentage of vaccination equals less morbidity and mortality, achieving this goal is not an easy task. Many countries face economic, cultural, and political challenges. To vaccinate sufficient numbers of people, vaccines must be available, convenient, and affordable. Nevertheless, despite the availability of vaccines, some people are reluctant or hesitant to be vaccinated [17, 18]. Previous findings showed that different factors could lead to COVID-19 vaccine hesitancy. Public distrust in the vaccine and its efficiency, lack of trust, belief that the vaccine has a political and harmful nature, and concerns about its safety are among the critical factors [1921]. In addition, the overwhelming amount of misinformation on social media has made it harder for people to trust the vaccine [22, 23]. In many countries, vaccine hesitancy is high enough to endanger community immunity [18].

Iran (and other countries worldwide) began its vaccination program against COVID-19 on the 9th of February 2021 and accelerated it in September 2021 until 76.47% coverage (at least one dose) was achieved on the 12th of September 2022 [24]. The program was designed so that vaccination could be available for all of the population despite challenges. Vaccines were free and could be administered on-site to people who could not show up to vaccination centers or to nomads living far from the reach of health centers through mobile health managers. Those who did not show up for vaccination were called to be reminded of where and how they could receive the vaccines. Because it is crucial to understand the determinants of rejecting the vaccine despite its availability throughout the country while more vaccination equals less mortality and morbidity, this cross-sectional study was conducted in the fifth largest city of Iran. The findings of the current study will help local and global health authorities take the necessary actions for achieving healthier communities.

Methods and materials

This cross-sectional study was conducted between March 8th, 2022, and April 15th, 2022, to investigate the factors associated with reluctance toward COVID-19 vaccination among those who had already been called in Shiraz, the fifth most populous city in the south-west of Iran.

Sample size

The sample size was calculated to be 800 with a 95% confidence interval, 0.5% margin of error, 25% expected agreement, and the expected population size of 629,115 out of 3,583,549 who were eligible for vaccination as provided by the Vice-chancellor for Health.

Sampling method

Personal and contact information for prospective participants was obtained with the help of the Vice-chancellor for Health, affiliated with Shiraz University of Medical Sciences (SUMS); the individuals were contacted by phone and requested to complete the relevant questionnaire until a sample size of 800 individuals was attained.

Ethics approval and consent to participate

The Medical Ethics Committee of Shiraz University of Medical Sciences approved the present study with the code number IR.SUMS.REC.1400.814. The purpose of this study was thoroughly explained to the participants, and they were assured that their information would be kept confidential by the researchers. Verbal consent was also obtained from the participants.

Inclusion and exclusion criteria

Inclusion criteria included being above 18 years of age, registered as inhabitants of Shiraz in the Fars Civil Registry Office, and not having referred for vaccination against COVID-19, even after having been called. Individuals who did not answer their phone after attempts were made on three different weekdays at various hours of the day or did not consent to participate in the survey and those who had been vaccinated in other countries were excluded from this study.

Data gathering tool

The questionnaire used in the current study was designed based on a literature review and expert opinion and consisted of five parts: 1. Demographic features of participants and self-reported socio-economic status. 2. A self-rated health score between 0–10 (0 equaling poor health and 10 equaling excellent health) and a score of presumed susceptibility to COVID-19 infection between 0–10 (0 equaling low susceptibility and 10 equaling high susceptibility) 3. Questions regarding their reluctance toward vaccination against COVID-19 and motivation to participate in the vaccination program. 4. Source of information on reluctance to vaccinate. 5. The methods used by participants to prevent COVID-19 contraction.

Study area

The current study was conducted in Shiraz, the capital of Fars province, located in southern Iran. Shiraz’s 2022 metropolitan population was estimated to be 1,700,000, making it the fifth most populated city in Iran. With 41 hospitals and nearly 100 local health centers delivering primary health care, Shiraz is considered a center for health service delivery in southern Iran. Since February 2021, all local health centers throughout the metropolitan area of the city have offered vaccination with different types of vaccines, including domestic (COVIran Barekat, SpikoGen, PastoCoVac, RaziCovPars) and non-domestic ones (Sinopharm, Sputnik, AstraZeneca, COVAXIN). As of August 2022, all people above 18 years of age can receive their fourth dose of the vaccine in listed health centers.

Data analysis

Descriptive statistics such as mean, standard deviation, and frequency distribution tables will be applied to describe the results. The chi-square or Fisher’s exact test was used to compare the existing data, and p-values of less than 0.05 were considered significant. All data was analyzed using Statistical Package for Social Sciences (SPSS Inc., Chicago, Illinois, USA) version 26.0 software.

Results

Out of 801 participants in the current study, 427 (53.3%) were men, and 502 (62.7%) were married. Mean participant age was 37.92 years (± 14.16), and participants had a mean number of 2.27 (± 1.69) children. Most of the participants were of Iranian nationality (95.4%), Fars ethnicity (74.8%), had a high school diploma (38.3%), and without supplementary insurance coverage (51.8%). The mean score of self-rated health was reported as 8.40 out of 10 (±1.93), and the mean score of presumed susceptibility to COVID-19 infection was reported as 4.64 out of 10 (± 2.80) (Table 1).

Table 1. Demographic characteristics of those reluctant toward vaccination in Shiraz city in 2022.

Variable Subgroup Frequency Percent (%) *
Gender Male 427 53.3
Female 374 46.7
Marital status Single 258 32.0
Married 502 62.7
Widowed 25 3.1
Divorced 16 2
Highest education attainment Illiterate 82 10.3
Below high school diploma 302 37.8
High school diploma 306 38.3
University degree 110 13.8
Nationality Iranian 764 95.4
Non-Iranian 37 4.6
Ethnicity Fars 591 74.8
Turk 95 12
Lor 65 8.2
Others 39 4.8
Supplementary insurance coverage No 415 51.8
Yes 386 48.2
Socio-economic status Middle to high 352 43.9
Middle to low 92 11.5
Low 357 44.6

*Percentage = frequency/801*100

In the current study, 302 participants (37.7%) reported at least one incident of COVID-19 contraction, which led to the hospitalization of 15 (5%) individuals. In the majority of cases, COVID-19 contraction was diagnosed by a physician (181; 22.5%) or confirmed by Polymerase Chain Reaction (PCR) test (83; 10.3%). Fig 1.

Fig 1. Methods used to diagnose COVID-19 in 301 participants who reported at least one COVID-19 infection.

Fig 1

PCR: Polymerase Chain Reaction; CT scan: Computed tomography scan.

As shown in Fig 2, the primary sources of information regarding the COVID-19 vaccine were family members and close friends (439; 54.8%), social media including Instagram, WhatsApp, Twitter, and Facebook (231, 28.8%), and national broadcasting (111, 13.9%).

Fig 2. Primary sources of information about the COVID-19 vaccine by the number of respondents.

Fig 2

The current findings revealed that 350 (43.7%) participants claimed the side effects of the vaccine outweighed the benefits as one of their reasons for reluctance toward COVID-19 vaccination, followed by the unknown efficacy of vaccines (40.4%) and a lack of trust in vaccine companies (32.8%). The reasons for vaccine reluctance are summarized in Table 2.

Table 2. Reasons for reluctance toward COVID-19 vaccination.

Reasons for reluctance Frequency; N = 801 Percent (%)
The side effects of the vaccine outweigh the benefits. 350 43.7
The efficacy of vaccines is unknown. 324 40.4
I do not trust vaccine companies. 263 32.8
My body has a robust immune system. 190 23.7
I do not need to get the vaccine because of mask and glove use. 105 13.1
Life is in the hands of God, and there is no need for a vaccine. 35 4.4
I refuse due to pregnancy or lactation. 34 4.2
The vaccine I trust is not available. 31 3.9
I have no time to get vaccinated. 30 3.7
Health authorities’ speech about vaccines is contradictory. 28 3.5
I have experienced reactions to previous vaccines. 28 3.5
I do not believe in the existence of COVID-19. 27 3.4
COVID-19 is not as intense as broadcasted. 27 3.4
I have already contracted COVID-19, so I do not need vaccination. 26 3.2
I trust the anti-vaxxers. 20 2.5
My decision is based on my physician’s opinion. 15 1.9
I have a medical condition. 13 1.6
I believe in a conspiracy theory. 6 0.7
Vaccination contradicts my religious beliefs. 3 0.4
Other 265 33.0

When asked under what conditions would they participate in the vaccination program, participants reported assurance of the safety of the vaccine (43.7%) and assurance of the effectiveness of the vaccine (34.5%) most frequently. An additional 204 (25.1%) participants claimed they would not get vaccinated under any circumstances (Table 3).

Table 3. Response rate to the question "Under what conditions will you participate in the vaccination program?" among the unvaccinated population in Shiraz, Iran.

Reasons to participate in the future. Frequency; N = 801 Percent (%)
I am assured of the safety of the vaccine. 350 43.7
I am assured of the effectiveness of the vaccine. 276 34.5
I will not get vaccinated under any circumstances. 204 25.5
I need access to the desired vaccine. 90 11.2
I need secure access to approved non-domestic vaccines. 39 4.9
I need secure access to approved domestic vaccines 19 2.4
I will vaccinate after pregnancy and lactation 21 2.6
I will vaccinate if my physician advises me thus. 14 1.7
Others 154 19.2

Fig 3 demonstrates the methods used by participants who were reluctant to vaccination to prevent COVID-19 contraction.

Fig 3. Response rate to the question of "What do you do to prevent contracting COVID-19?" among the unvaccinated population in Shiraz, Iran.

Fig 3

As can be seen in Table 4, the male gender was significantly associated with reluctancy toward vaccination due to self-presumption of high immunity (p-value < 0.001), use of mask, gloves, and sanitizers (p-value = 0.021), disbelief in the existence of COVID-19 (p-value = 0.003), unavailability of the desired vaccine (p-value = 0.006), and belief that COVID-19 is not as severe as broadcasted (p-value = 0.010).

Table 4. Association of age and gender with reluctancy towards coronavirus disease vaccination and the motivation to participate in vaccination among the general population of Shiraz.

Reason Gender; n (%) Age group; n (%)
Male; n = 427 Female; n = 374 P-value* 18–25; n = 155 26–45; n = 415 46–65; n = 178 > 65; n = 38 P-value*
Reluctancy toward vaccination
The side effects of the vaccine outweigh the benefits. 185 (43.3) 165 (44.1) 0.822 69 (44.5) 179 (43.1) 80 (44.9) 16 (42.1) 0.970
The efficacy of vaccines is unknown. 184 (43.1) 140 (37.4) 0.104 68 (43.9) 163 (39.3) 75 (42.1) 12 (31.6) 0.486
I distrust vaccine companies. 141 (33.0) 122 (32.6) 0.904 51 (32.9) 137 (33.0) 58 (32.6) 15 (39.5) 0.869
My body has a robust immune system. 123 (28.8) 67 (17.9) <0.001 42 (27.1) 108 (26.0) 33 (18.5) 4 (10.5) 0.037
I do not need to get the vaccine because of mask and glove use. 67 (15.7) 38 (10.2) 0.021 23 (14.8) 59 (14.2) 17 (9.6) 3 (7.9) 0.289
Life is in the hands of God, and there is no need for a vaccine. 24 (5.6) 11 (2.9) 0.064 1 (0.6) 19 (4.6) 12 (6.7) 3 (7.9) 0.036
I refuse due to pregnancy or lactation. 0 (0.0) 34 (9.1) <0.001 8 (5.2) 26 (6.3) 0 (0.0) 0 (0.0) 0.003
The vaccine I trust is not available. 24 (5.6) 7 (1.9) 0.006 5 (3.2) 18 (4.3) 6 (3.4) 0 (0.0) 0.554
I have no time to get vaccinated. 21 (4.9) 9 (2.4) 0.062 9 (5.8) 21 (5.1) 0 (0.0) 0 (0.0) 0.007
Health authorities’ speech about vaccines is contradictory. 18 (4.2) 10 (2.7) 0.236 4 (2.6) 19 (4.6) 5 (2.8) 0 (0.0) 0.337
I have experienced reactions to previous vaccines. 16 (57.1) 12 (3.2) 0.679 5 (3.2) 15 (3.6) 7 (3.9) 0 (0.0) 0.672
I do not believe in the existence of COVID-19. 22 (5.2) 5 (1.3) 0.003 2 (1.3) 14 (3.4) 9 (5.1) 2 (5.3) 0.267
COVID-19 is not as intense as broadcasted. 21 (4.9) 6 (1.6) 0.010 4 (2.6) 19 (4.6) 4 (2.2) 0 (0.0) 0.252
I have already contracted COVID-19, so there is no need for a vaccination. 16 (3.7) 10 (2.7) 0.392 3 (1.9) 18 (4.3) 4 (2.2) 1 (2.6) 0.397
I trust the anti-vaxxers. 12 (2.8) 8 (2.1) 0.544 9 (5.8) 9 (2.2) 1 (0.6) 0 (0.0) 0.022
Participation in vaccination
I require assurance of the safety of the vaccine. 169 (39.6) 181 (48.4) 0.012 63 (40.6) 182 (43.9) 83 (46.6) 15 (39.5) 0.685
I require assurance of the effectiveness of the vaccine. 136 (31.9) 140 (37.4) 0.097 58 (37.4) 140 (33.7) 61 (34.3) 13 (34.2) 0.875
I will not get vaccinated under any circumstances. 140 (32.8) 64 (17.1) <0.001 38 (24.5) 103 (24.8) 47 (26.4) 12 (31.6) 0.802
I require access to the desired vaccine. 49 (11.5) 41 (11.0) 0.819 21 (13.5) 59 (14.2) 8 (4.5) 0 (0.0) 0.001
I require secure access to approved non-domestic vaccines. 20 (4.7) 19 (5.1) 0.795 11 (7.1) 22 (5.3) 5 (2.8) 1 (2.6) 0.285
I require secure access to approved domestic vaccines. 6 (1.4) 13 (3.5) 0.055 6 (3.9) 10 (2.4) 2 (1.1) 1 (2.6) 0.447
I will vaccinate if my physician advises me thus. 5 (1.2) 9 (2.4) 0.183 1 (0.6) 6 (1.4) 6 (3.4) 1 (2.6) 0.221

* Chi-square/Fisher exact test

Bold variables indicate a significant association.

The female gender was significantly associated with future participation in the vaccination program if assurance of the common side effects of vaccines was provided (p-value = 0.012). In contrast, the male gender was significantly associated with never participating in vaccination under any circumstances (p-value < 0.001).

Aged between 18 and 25 years was significantly associated with reluctance toward vaccination because of self-presumed high immunity (p-value = 0.037) and trust of anti-vaxxers (p-value = 0.022). Furthermore, participants above 65 years of age believed that they should accept their destiny and thus felt that vaccination was not required (p-value = 0.036).

The current results revealed that female participants tended to get information about the COVID-19 vaccine from healthcare workers (p-value < 0.001). Male participants, however, tended to be informed through social media (p-value < 0.001) and radio and TV (p-value < 0.001) and believed in their own opinion rather than those of others (p-value = 0.006).

As shown in Table 5, participants with university degrees were significantly more reluctant toward vaccination because of contradiction in health authorities’ speech about vaccination (p-value = 0.014); they were willing to participate in a vaccination program if foreign vaccines were available (p-value = 0.005). An education level below a high school diploma was significantly associated with reluctance toward vaccination because of the unavailability of the desired vaccine (p-value = 0.041) and belief that life is in the hands of God, so vaccination is not required (p-value = 0.010).

Table 5. Association of educational level and social-economic status with reluctance towards coronavirus disease vaccination and motivations for participation in vaccination among the general population of Shiraz.

Reason Educational level; n (%) Socio-economic status; n (%)
Illiterate; n = 82 Below high school diploma; n = 302 High school diploma; n = 306 University degrees; n = 110 P-value* Middle to high; n = 352 Middle to low; n = 92 Low; n = 357 P-value*
Reluctancy toward vaccination
The side effects of the vaccine outweigh the benefits. 29 (35.4) 132 (43.7) 145 (47.4) 44 (40.0) 0.202 130 (36.9) 24 (26.1) 196 (54.9) <0.001
The efficacy of vaccines is unknown. 25 (30.5) 118 (39.1) 133 (43.5) 48 (43.6) 0.156 109 (31.0) 27 (29.3) 188 (52.7) <0.001
I mistrust vaccine companies. 19 (23.2) 101 (33.4) 105 (34.3) 38 (34.5) 0.265 87 (24.7) 10 (10.9) 166 (46.5) <0.001
My body has a robust immune system. 13 (15.9) 73 (24.2) 78 (25.5) 26 (23.6) 0.339 61 (17.3) 18 (19.6) 111 (31.1) <0.001
I do not need to get the vaccine because of mask and glove use. 6 (7.3) 47 (15.6) 44 (14.4) 8 (7.3) 0.052 20 (5.7) 4 (4.3) 81 (22.7) <0.001
Life is in the hands of God, and there is no need for a vaccine. 1 (1.2) 22 (7.3) 11 (3.6) 1 (0.9) 0.010 11 (3.1) 1 (1.1) 23 (6.4) 0.025
I refuse due to pregnancy or lactation. 2 (2.4) 7 (2.3) 17 (5.6) 8 (7.3) 0.063 20 (5.7) 7 (7.6) 7 (2.0) 0.011
The vaccine I trust is not available. 0 (0.0) 18 (6.0) 11 (3.6) 2 (1.8) 0.041 8 (2.3) 0 (0.0) 23 (6.4) 0.002
I have no time to get vaccinated. 7 (8.5) 11 (3.6) 12 (3.9) 0 (0.0) 0.014 19 (5.4) 3 (3.3) 8 (2.2) 0.083
Health authorities’ speech about vaccines is contradictory 1 (1.2) 7 (2.3) 10 (3.3) 10 (9.1) 0.014 7 (2.0) 2 (2.2) 19 (5.3) 0.041
I have experienced reactions to previous vaccines. 2 (2.4) 12 (4.0) 9 (2.9) 4 (3.6) 0.861 8 (2.3) 2 (2.2) 18 (5.0) 0.102
I disbelieve in the existence of COVID-19. 3 (3.7) 14 (4.6) 8 (2.6) 2 (1.8) 0.415 10 (2.8) 4 (4.3) 13 (3.6) 0.721
COVID-19 is not as intense as broadcasted. 1 (1.2) 14 (4.6) 10 (3.3) 2 (1.8) 0.402 12 (3.4) 3 (3.3) 12 (3.4) 0.997
I have already contracted COVID-19, so there is no need for a vaccination. 1 (1.2) 7 (2.3) 9 (2.9) 9 (8.2) 0.032 13 (3.7) 3 (3.3) 1 (2.8) 0.799
I trust anti-vaxxers. 1 (1.2) 3 (1.0) 11 (3.6) 5 (4.5) 0.062 7 (2.0) 6 (6.5) 7 (2.0) 0.031
Participation in vaccination
I require assurance of the safety of the vaccine. 31 (37.8) 136 (45.0) 142 (46.4) 41 (37.3) 0.248 137 (38.9) 23 (25.0) 190 (53.2) <0.001
I require assurance of the effectiveness of the vaccine. 25 (30.5) 98 (32.5) 116 (37.9) 37 (33.6) 0.431 83 (23.6) 19 (20.7) 174 (48.7) <0.001
I will not get vaccinated under any circumstances. 17 (20.7) 76 (25.5) 80 (26.1) 31 (28.2) 0.686 95 (27.0) 31 (33.7) 78 (21.8) 0.046
I require access to the desired vaccine. 9 (11.0) 28 (9.3) 39 (12.7) 14 (12.7) 0.549 11 (3.1) 4 (4.3) 75 (21.0) <0.001
I require secure access to approved non-domestic vaccines. 1 (1.1) 8 (2.6) 19 (6.2) 11 (10.0) 0.005 24 (6.8) 3 (3.3) 12 (3.4) 0.076
I require secure access to approved domestic vaccines. 2 (2.4) 4 (1.3) 11 (3.6) 2 (1.8) 0.314 6 (1.7) 1 (1.1) 12 (3.4) 0.241
I will vaccinate if my physician advises me thus. 1 (1.2) 7 (2.3) 2 (0.7) 3 (2.7) 0.304 10 (2.8) 0 (0.0) 4 (1.1) 0.086

* Chi-square/Fisher exact test

Bold variables indicate a significant association.

Figs 4 and 5 demonstrate the reasons for reluctancy toward vaccination and factors influencing participation in vaccination based on socio-economic status in the unvaccinated population of this study.

Fig 4. Reasons for reluctancy toward vaccination based on socio-economic status among the unvaccinated population in Shiraz, Iran.

Fig 4

Fig 5. Factors influencing participation in vaccination based on socio-economic status among the unvaccinated population in Shiraz, Iran.

Fig 5

Those participants who reported their economic status as low were significantly reluctant toward vaccination because of self-presumption of high immunity (p-value < 0.001), unclear efficacy of vaccines (p-value < 0.001), the side effects outweighing the benefits of vaccines (p-value < 0.001), having no trust in vaccine companies (p-value < 0.001), the usage of mask, gloves, and sanitizers (p-value < 0.001), the contradictory speech of health authorities about vaccines (p-value = 0.041), and the unavailability of trusted vaccines (p-value = 0.002). Low socioeconomic status was significantly associated with participation in vaccination programs if participants were assured of the safety (p-value < 0.001) and efficacy (p-value < 0.001) of vaccines and upon the availability of preferred ones (p-value < 0.001). Moreover, those who reported their socio-economic status as lower than average were more likely to never get the vaccination (p-value = 0.046). It should also be noted that people with low socio-economic status were more likely to obtain information about vaccine reluctance from family and friends (p-value <0.001) and complementary medical professionals (p-value <0.001).

Discussion

The benefits of immunization undeniably outweigh the side effects, as it is one of the most influential and cost-benefit interventions in improving health status among individuals [25]. Achieving a high vaccination rate is required to reduce the morbidity and mortality in preventable diseases with immunization [25]. Keeping in mind that vaccine development for the newly emerged disease is the first challenge to lessening its effect on public health, dealing with vaccination hesitancy and reluctance is the next battle. This phenomenon has held back the global effort toward better health, as evidenced by the re-emergence of some contagious diseases such as pertussis and measles [26, 27]. It is considered one of the top ten threats to global health in 2019 by the WHO [28]. Vaccine hesitancy is a complex problem, and there is no single intervention to prevent it; understanding the roots and causes of this phenomenon in subgroups might provide sufficient information to help authorities take necessary actions when implementing health policies.

In the current study, we evaluated the reasons for being reluctant toward vaccination, the factors that are important for individuals to participate in vaccination programs, and their associations with demographic characteristics despite their variety and availability. The results demonstrate that two significant factors prevent people from vaccinating, namely concern about vaccine efficacy and concern about side effects. Men and younger generations (18–25 years of age) tend to be more reluctant toward vaccination because of their presumption of high immunity status. Those with low socioeconomic status who primarily get their information about COVID-19 from family and friends were more reluctant toward vaccination because of concerns regarding efficacy, side effects, and not trusting the vaccine companies. Similar results have also been reported regarding low socio-economic status and age group [29, 30]. Moreover, those with university degrees were more reluctant toward vaccination because of contradictions in health authorities’ speech; they were willing to participate in vaccination programs if foreign vaccines became available. Nonetheless, these factors may differ among different nations and cultures. For example, Umakanthan et al. investigated vaccine hesitancy in Germany and reported that younger age, lower education, and female gender decreased the odds of having the willingness to vaccinate [31].

Several studies have investigated the roots of vaccine hesitancy in the COVID-19 era, and most found concerns about efficacy and safety to be the most highly reported causes, similar to the present study [3235]; however, those studies were conducted mainly in late 2020 and early 2021, when COVID-19 vaccination was not as adequately administered compared to the timeline of the current study, when Iran, similar to many other countries, was offering their citizens the fourth dose of COVID-19 vaccine. Nevertheless, the trend toward vaccine reluctance is being reduced as time passes [36, 37], and to date billions of people have been inoculated with vaccines that have proven their efficacy and safety, even toward new COVID-19 variants [38]. However, the remaining unvaccinated population is still concerned about vaccine effectiveness and security, and this situation requires increasing awareness in the public, primarily through person-to-person communications and social media, which were reported as the most frequent sources of information in the present study.

This study and others emphasize the importance of implementing policies toward a higher vaccine coverage rate equal to less morbidity and mortality and fewer adverse effects on various aspects of people’s life, including social, mental, economic, and cultural dimensions. Because vaccine reluctance is a psycho-behavioral issue and may differ from one society to another based on beliefs, cultural and educational differences of populations, authorities must take the proper actions to deal with this problem reasonably, as it is not an issue related solely to COVID-19 [31]. Thus, we recommend further studies evaluating vaccine hesitancy and reluctance to be adjusted based on an organization consisting of a multidisciplinary panel of experts, especially in population hot spots [35], while periodically performing surveys in the targeted groups to understand better subgroups involved in vaccine reluctance in the present study.

Knowing that vaccine reluctance is related to ineffective communication and mass population education, this organization can learn from other countries’ experiences in dealing with vaccine hesitancy to implement policies considering the targeted sub-groups’ socio-cultural beliefs and establish the method that has worked in previous battles against this issue. Policymakers can take advantage of numerous tactics mentioned in the scientific literature while combating vaccine reluctance. For instance, the Council of Canadian Academies Expert Panel on Health Product Risk Communication Evaluation has addressed the five best practices to combat vaccine hesitancy: (I) Detect the targeted population and establish trust; (II) Provide balanced, evidence-based information regarding both the risks and benefits of being vaccinated; (III) Provide facts and address misconceptions and myths; (IV) Utilize visual-aid tools such as videos, pictures, and graphs, as they help people with little numeracy skills; (V) Test the designed communication toolkit before launching [39]. Nevertheless, it should be noted that although this method might have worked in Canada, there is no guarantee of its efficacy in Iran, as there are many socio-cultural differences between the two countries.

Some limitations faced by the current study are worth mentioning. Only individuals above 18 years of age were included, so there is no data regarding the hesitancy of those under 18 years of age or the attitude of their parents toward vaccination. Moreover, the influence of available treatments and the availability and company of vaccines were not discussed, as many individuals were reluctant toward vaccines because of the unavailability of desired ones, such as Pfizer-BioNTech, Moderna, and Johnson and Johnson, among others. Furthermore, as this study was based on a self-reporting questionnaire, it is susceptible to some biases, such as recall bias, that might affect the outcome of the results.

Conclusion

As demonstrated in the current study, avoiding vaccination is an undeniable public and individual health concern in Iran. Worrying about vaccine efficacy and side effects are the most reported causes of vaccine reluctance among individuals, which could be altered by emphasizing mass education and averting an infodemic by forming dedicated multidisciplinary organizations. Therefore, health authorities must take action and combat vaccine reluctance to increase vaccination awareness, especially among vulnerable groups.

Acknowledgments

This study was the subject of the MPH degree thesis for Parisa Hossseinpour and Amirhossein Erfani.

Abbreviations

COVID-19

Coronavirus disease of 2019

WHO

World Health Organization

FDA

Food and Drug Administration

Data Availability

All data regarding this study has been reported in the paper. Don't hesitate to get in touch with the corresponding author in case further information is required.

Funding Statement

Vice-chancellor for Research of Shiraz University of Medical Sciences financially supported this Study through Kamran Bagheri Lankarani (Grant No: 24974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

  • 1.Afolabi AA, Ilesanmi OS. Dealing with vaccine hesitancy in Africa: the prospective COVID-19 vaccine context. Pan Afr Med J. 2021;38:3. Epub 2021/02/02. doi: 10.11604/pamj.2021.38.3.27401 ; PubMed Central PMCID: PMC7825371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Umakanthan S, Sahu P, Ranade AV, Bukelo MM, Rao JS, Abrahao-Machado LF, et al. Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Postgrad Med J. 2020;96(1142):753–8. Epub 2020/06/22. doi: 10.1136/postgradmedj-2020-138234 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Shahriarirad R, Khodamoradi Z, Erfani A, Hosseinpour H, Ranjbar K, Emami Y, et al. Epidemiological and clinical features of 2019 novel coronavirus diseases (COVID-19) in the South of Iran. BMC Infect Dis. 2020;20(1):427. Epub 2020/06/20. doi: 10.1186/s12879-020-05128-x ; PubMed Central PMCID: PMC7301075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19–11 March 2020. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020
  • 5.Bagchi B, Chatterjee S, Ghosh R, Dandapat D. Impact of COVID-19 on global economy. Coronavirus Outbreak and the Great Lockdown: Springer; 2020. p. 15–26. [Google Scholar]
  • 6.Umakanthan S, Bukelo MM, Gajula SS. The Commonwealth Caribbean COVID-19: Regions Resilient Pathway During Pandemic. Front Public Health. 2022;10:844333. Epub 2022/06/07. doi: 10.3389/fpubh.2022.844333 ; PubMed Central PMCID: PMC9160791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Umakanthan S, Senthil S, John S, Madhavan MK, Das J, Patil S, et al. The effect of statins on clinical outcome among hospitalized patients with COVID-19: a multi-centric cohort study. 2022:2558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Shahriarirad R, Erfani A, Ranjbar K, Bazrafshan A, Mirahmadizadeh A. The mental health impact of COVID-19 outbreak: a Nationwide Survey in Iran. Int J Ment Health Syst. 2021;15(1):19. Epub 2021/03/01. doi: 10.1186/s13033-021-00445-3 ; PubMed Central PMCID: PMC7913044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.VoPham T, Weaver MD, Hart JE, Ton M, White E, Newcomb PA. Effect of social distancing on COVID-19 incidence and mortality in the US. medRxiv. 2020. Epub 2020/06/27. doi: 10.1101/2020.06.10.20127589 ; PubMed Central PMCID: PMC7310657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586(7830):516–27. Epub 2020/09/24. doi: 10.1038/s41586-020-2798-3 . [DOI] [PubMed] [Google Scholar]
  • 11.World Health Organization. Coronavirus disease (COVID-19): Vaccines. URL: https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-(covid-19)-vaccines
  • 12.Thanapluetiwong S, Chansirikarnjana S, Sriwannopas O, Assavapokee T, Ittasakul P. Factors associated with COVID-19 Vaccine Hesitancy in Thai Seniors. Patient Prefer Adherence. 2021;15:2389–403. Epub 2021/11/11. doi: 10.2147/PPA.S334757 ; PubMed Central PMCID: PMC8568699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Callaway EJN. COVID vaccine excitement builds as Moderna reports third positive result. 2020;587(7834):337–9. [DOI] [PubMed] [Google Scholar]
  • 14.Knoll MD, Wonodi CJTL. Oxford–AstraZeneca COVID-19 vaccine efficacy. 2021;397(10269):72–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Cook TM, Roberts JV. Impact of vaccination by priority group on UK deaths, hospital admissions and intensive care admissions from COVID-19. Anaesthesia. 2021;76(5):608–16. Epub 2021/02/12. doi: 10.1111/anae.15442 ; PubMed Central PMCID: PMC8013188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.World Health Organization. Coronavirus disease (COVID-19): Herd immunity, lockdowns and COVID-19. URL: https://www.who.int/news-room/questions-and-answers/item/herd-immunity-lockdowns-and-covid-19
  • 17.Fisher KA, Bloomstone SJ, Walder J, Crawford S, Fouayzi H, Mazor KMJAoim. Attitudes toward a potential SARS-CoV-2 vaccine: a survey of US adults. 2020;173(12):964–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Askarian M, Semenov A, Llopis F, Rubulotta F, Dragovac G, Pshenichnaya N, et al. The COVID-19 vaccination acceptance/hesitancy rate and its determinants among healthcare workers of 91 Countries: A multicenter cross-sectional study. 2022;21:93. doi: 10.17179/excli2021-4439 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Heidari M, Jafari H. Challenges of COVID-19 Vaccination in Iran: In the Fourth Wave of Pandemic Spread. Prehosp Disaster Med. 2021;36(5):659–60. Epub 2021/07/22. doi: 10.1017/S1049023X21000777 ; PubMed Central PMCID: PMC8365040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Mohapatra PR, Mishra BJTLID. Regulatory approval of COVID-19 vaccine for restricted use in clinical trial mode. 2021;21(5):599–600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Troiano G, Nardi A. Vaccine hesitancy in the era of COVID-19. Public Health. 2021;194:245–51. Epub 2021/05/10. doi: 10.1016/j.puhe.2021.02.025 ; PubMed Central PMCID: PMC7931735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Wilson SL, Wiysonge C. Social media and vaccine hesitancy. BMJ Glob Health. 2020;5(10):e004206. Epub 2020/10/25. doi: 10.1136/bmjgh-2020-004206 ; PubMed Central PMCID: PMC7590343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Burki TJTLDH. Vaccine misinformation and social media. 2019;1(6):e258–e9. [Google Scholar]
  • 24.covidvax.live: Live COVID-19 Vaccination Tracker. URL: https://covidvax.live/location/irn
  • 25.Eskola J, Duclos P, Schuster M, MacDonald NEJV. How to deal with vaccine hesitancy? 2015;33(34):4215–7. [DOI] [PubMed] [Google Scholar]
  • 26.Phadke VK, Bednarczyk RA, Salmon DA, Omer SBJJ. Association between vaccine refusal and vaccine-preventable diseases in the United States: a review of measles and pertussis. 2016;315(11):1149–58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Benecke O, DeYoung SE. Anti-Vaccine Decision-Making and Measles Resurgence in the United States. Glob Pediatr Health. 2019;6:2333794X19862949. Epub 2019/08/07. doi: 10.1177/2333794X19862949 ; PubMed Central PMCID: PMC6657116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.World Health Organization. Ten health issues WHO will tackle this year. 2019. URL: https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019 [Google Scholar]
  • 29.Bajos N, Spire A, Silberzan L, group Es. The social specificities of hostility toward vaccination against Covid-19 in France. PLoS One. 2022;17(1):e0262192. Epub 2022/01/07. doi: 10.1371/journal.pone.0262192 ; PubMed Central PMCID: PMC8735622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Puteikis K, Mameniškienė RJIjoer, health p. Factors associated with COVID-19 vaccine hesitancy among people with epilepsy in Lithuania. 2021;18(8):4374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Umakanthan S, Lawrence S. Predictors of COVID-19 vaccine hesitancy in Germany: a cross-sectional, population-based study. Postgrad Med J. 2022;98(1164):756–64. Epub 2022/02/05. doi: 10.1136/postgradmedj-2021-141365 ; PubMed Central PMCID: PMC8822538. [DOI] [PubMed] [Google Scholar]
  • 32.Soares P, Rocha JV, Moniz M, Gama A, Laires PA, Pedro AR, et al. Factors Associated with COVID-19 Vaccine Hesitancy. Vaccines (Basel). 2021;9(3):300. Epub 2021/04/04. doi: 10.3390/vaccines9030300 ; PubMed Central PMCID: PMC8004673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Alzahrani SH, Baig M, Alrabia MW, Algethami MR, Alhamdan MM, Alhakamy NA, et al. Attitudes toward the SARS-CoV-2 vaccine: results from the Saudi Residents’ Intention to Get Vaccinated against COVID-19 (SRIGVAC) study. 2021;9(7):798. doi: 10.3390/vaccines9070798 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.King WC, Rubinstein M, Reinhart A, Mejia R. Time trends, factors associated with, and reasons for COVID-19 vaccine hesitancy: A massive online survey of US adults from January-May 2021. PLoS One. 2021;16(12):e0260731. Epub 2021/12/22. doi: 10.1371/journal.pone.0260731 ; PubMed Central PMCID: PMC8691631 Reinhart received salary support from an unrestricted gift from Facebook described in the funding section of the paper. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Umakanthan S, Patil S, Subramaniam N, Sharma RJV. COVID-19 vaccine hesitancy and resistance in India explored through a population-based longitudinal survey. 2021;9(10):1064. doi: 10.3390/vaccines9101064 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Rane MS, Kochhar S, Poehlein E, You W, Robertson MM, Zimba R, et al. Determinants and Trends of COVID-19 Vaccine Hesitancy and Vaccine Uptake in a National Cohort of US Adults: A Longitudinal Study. Am J Epidemiol. 2022;191(4):570–83. Epub 2022/01/10. doi: 10.1093/aje/kwab293 ; PubMed Central PMCID: PMC8755394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Willingness to get vaccinated against COVID-19. URL: https://ourworldindata.org/grapher/covid-vaccine-willingness-and-people-vaccinated-by-month?country=~FRA
  • 38.Huang Z, Su Y, Zhang T, Xia N. A review of the safety and efficacy of current COVID-19 vaccines. Front Med. 2022;16(1):39–55. Epub 2022/02/06. doi: 10.1007/s11684-021-0893-y ; PubMed Central PMCID: PMC8815389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Hastall MR, Koinig I, Kunze U, Meixner O, Sachse K, Wurzner R. Multidisciplinary expert group: communication measures to increase vaccine compliance in adults. Wien Med Wochenschr. 2022:1–4. Epub 2022/07/07. doi: 10.1007/s10354-022-00946-x ; PubMed Central PMCID: PMC9258758. [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Srikanth Umakanthan

5 Oct 2022

PONE-D-22-26777Associated Factors of Reluctancy Toward COVID-19 Vaccination; A Cross-Sectional Study in Shiraz, Southern Iran ​PLOS ONE

Dear Dr. Amirhossein Erfani,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Nov 19 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Srikanth Umakanthan

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service. 

 Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. Both organizations have experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. To take advantage of our partnership with AJE, visit the AJE website (http://aje.com/go/plos) for a 15% discount off AJE services. To take advantage of our partnership with Editage, visit the Editage website (www.editage.com) and enter referral code PLOSEDIT for a 15% discount off Editage services. If the PLOS editorial team finds any language issues in text that either AJE or Editage has edited, the service provider will re-edit the text for free.

 Upon resubmission, please provide the following: 

 ● The name of the colleague or the details of the professional service that edited your manuscript

 ● A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a *supporting information* file)

 ● A clean copy of the edited manuscript (uploaded as the new *manuscript* file)

3. Thank you for stating the following in the Acknowledgments Section of your manuscript: 

"This study was the subject of the MPH degree thesis for Parisa Hossseinpour and Amirhossein Erfani. The authors would like to thank the Vice Chancellor for Research of Shiraz University of Medical Sciences for financially supporting the project (Project code: 22574)."

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. 

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: 

"Vice-chancellor for Research of Shiraz University of Medical Sciences financially supported this Study through Kamran Bagheri Lankarani (Grant No: 24974)."

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript. 

5. Please include correct caption for figures.

6. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

The manuscript requires minor revisions as stated by the reviewers. Include a Point-to-point inclusion of the suggestions/comments to improvise the manuscript.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Well written manuscript that reflects the Associated Factors of Reluctancy Toward COVID-19 Vaccination in Iran.

The manuscript can be strengthened by incorporating the following points:

1. Include a short note on the origin of COVID-19 (refer and cite: doi: 10.1136/postgradmedj-2020-138234

2. Compare the COVID-19 states in Iran with other regions (refer and cite: doi: 10.3389/fpubh.2022.844333)

3. The role of vaccination status that has declined the vaccine resistance rates(refer and cite: doi: 10.3390/vaccines9101064.)

4. How the Iranian government and health care has imbibed regulations to combat COVID-19 targeting its predictors (refer and cite: doi: 10.1136/postgradmedj-2021-141365)

5. The treatment of COVID-19 and its implications on the vaccine hesitancy (refer and cite: doi: 10.3389/fphar.2022.742273.

6. Include other forms of representations in your figures (eg. Bar charts, histograms), color the images for better viewership.

Reviewer #2: The authors have finely incorporated the Associated Factors of Reluctancy Toward COVID-19 Vaccination in Iran.

Grammatical errors need to be corrected.

Include illustrations or bar charts. The introduction is very verbose. Needs to be tapered.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2022 Dec 12;17(12):e0278967. doi: 10.1371/journal.pone.0278967.r002

Author response to Decision Letter 0


23 Nov 2022

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Authors Response: We apologize for this inconvenience and have revised the manuscript based on the provided guidelines.

2. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service.

Authors Response: Our manuscript has been revised by a Native English editor and we have attached the certificate for your reference.

3. Upon resubmission, please provide the following:

● The name of the colleague or the details of the professional service that edited your manuscript

● A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a *supporting information* file)

● A clean copy of the edited manuscript (uploaded as the new *manuscript* file)

Authors Response: We have uploaded the mentioned files as requested.

4. Thank you for stating the following in the Acknowledgments Section of your manuscript:

"This study was the subject of the MPH degree thesis for Parisa Hossseinpour and Amirhossein Erfani. The authors would like to thank the Vice Chancellor for Research of Shiraz University of Medical Sciences for financially supporting the project (Project code: 22574)."

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "Vice-chancellor for Research of Shiraz University of Medical Sciences financially supported this Study through Kamran Bagheri Lankarani (Grant No: 24974)."

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Authors Response: We have moved the funding statement to the cover letter as requested.

5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

Authors Response: We have moved the ethical consideration section to the method and material section as requested.

6. Please include correct caption for figures.

Authors Response: We have adjusted and corrected the figure captions based on the journal’s guidelines.

7. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Authors Response: We have revised the manuscript reference list based on the journal’s guidelines.

Comments to the Author

Dear Editor and Reviewers,

Thanks for reaching out to us regarding the manuscript entitled “Associated Factors of Reluctancy Toward COVID-19 Vaccination; A Cross-Sectional Study in Shiraz, Southern Iran ". We believe that these comments have helped us enhance the quality of the manuscript. We also have done our best to revise and improve the paper according to the comments. Herewith, we provided the authors' responses to each comment right after each statement. Also, all the changes have been addressed in the manuscript through highlighted parts according to journal policies.

• Reviewer #1:

1. Include a short note on the origin of COVID-19 (refer and cite: doi: 10.1136/postgradmedj-2020-138234

Authors’ Response: Thank you for your comment. A statement regarding the origin of COVID-19 has been added to the manuscript according to the provided reference. (Lines 44 – 51)

2. Compare the COVID-19 states in Iran with other regions (refer and cite: doi: 10.3389/fpubh.2022.844333)

Author’s Response: Thank you for your comment and for providing us with this valuable article. A statement has been added to the manuscript addressing the economic effects of COVID-19. (Lines 47 – 51)

3. The role of vaccination status that has declined the vaccine resistance rates(refer and cite: doi: 10.3390/vaccines9101064.)

Authors’ Response: Thank you for your comment. This article was referred to in the discussion section regarding the concerns for the post-vaccine scare of adverse health effects. (Discussion; lines 266 – 268)

4. How the Iranian government and health care has imbibed regulations to combat COVID-19 targeting its predictors (refer and cite: doi: 10.1136/postgradmedj-2021-141365)

Authors’ Response: Thank you for the valuable comment. Since combating vaccine hesitancy might differ from one society to another, a statement regarding considering cultural beliefs and educational status was added to the manuscript. (Paragraph 2 Discussion section; lines 263 – 265; and Paragraph 4 discussion section; line 281 – 283)

5. The treatment of COVID-19 and its implications on the vaccine hesitancy (refer and cite: doi: 10.3389/fphar.2022.742273.

Authors’ Response: Thank you for your comment. Although we did not evaluate the effect of treatment on vaccine hesitancy, we have added this statement in the limitation section and also a statement regarding the practice of available medicines in combating the COVID-19 pandemic has been added to the manuscript (Lines 52 and 53).

6. Include other forms of representations in your figures (eg. Bar charts, histograms), color the images for better viewership.

Authors’ Response: Thank you for your comment. Two more figures regarding the reasons of reluctancy toward vaccination and influencing the of participation in vaccination based on socio-economic status has been added to the manuscript (Figure 4 and 5).

• Reviewer #2:

1. Grammatical errors need to be corrected.

Authors’ Response: Thank you for your valuable comment. The manuscript has been revised in aspect of grammatical errors by a professional English editor.

2. Include illustrations or bar charts.

Authors’ Response: Thank you for your comment. Two more figures regarding the reasons of reluctancy toward vaccination and influencing the of participation in vaccination based on socio-economic status has been added to the manuscript (Figure 4 and 5).

3. The introduction is very verbose. Needs to be tapered.

Authors’ Response: Thank you for your comment and concern. Based on the first reviewers comments we were obligated to add some additional requested information. Furthermore, we believe that any tapering in the information provided in the introduction section will interrupt the continuity and understanding of the phases and line of thought for the general readers. However, if the honorable reviewer believes that a certain part of the introduction is abundant, we would gladly revise the mentioned section accordingly.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Srikanth Umakanthan

25 Nov 2022

Factors associated with reluctancy to acquire COVID-19 vaccination: a cross-sectional study in Shiraz, Iran, 2022 ​

PONE-D-22-26777R1

Dear Dr. Erfani,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Srikanth Umakanthan

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Accept in revised format

Reviewers' comments:

Acceptance letter

Srikanth Umakanthan

2 Dec 2022

PONE-D-22-26777R1

Factors associated with reluctancy to acquire COVID-19 vaccination: a cross-sectional study in Shiraz,Iran, 2022 ​

Dear Dr. Erfani:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Srikanth Umakanthan

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    All data regarding this study has been reported in the paper. Don't hesitate to get in touch with the corresponding author in case further information is required.


    Articles from PLOS ONE are provided here courtesy of PLOS

    RESOURCES