Side effects of COVID-19 vaccines and perceptions about COVID-19 and its vaccines in Bangladesh: A Cross-sectional study

Highlights • Significant COVID-19 vaccine hesitancy exists globally, mainly due to safety concerns.• This study analyzed the side effects of COVID-19 vaccines in Bangladesh.• Less than half of those who received a COVID-19 vaccine experienced side effects.• The side effects were mild and regular and lasted 1–3 days only.• The findings demonstrate the safety of the COVID-19 vaccines.


Introduction
The COVID-19 pandemic has spread to every country on the planet, infecting nearly 270 million people and killing 5.4 million people as of December 11, 2021 [1]. COVID-19 0 s advent has had a disastrous influence on worldwide healthcare systems, with conse-quences in every facet of human life; leaving in its wake economic, familial, and mental health crises [2][3][4]. As a result, governments worldwide implemented border closures, travel bans, and quarantine protocols to stop the virus from spreading [4]. Unfortunately, the pandemic continues to hamper human lives across the globe.
Vaccines are thought to help the human body develop a longlasting immune response to fight infectious diseases effectively. Indeed, vaccination prevents about 2-3 million deaths each year [5]. Vaccine development, however, is not the final word in eradicating such a widespread and deadly disease [4]. Vaccine hesitancy has been and continues to be a significant threat to mass vaccination [6]. It is a growing public health problem fueled by misconceptions about vaccine safety and effectiveness [7][8][9]. The most common cause of vaccine hesitancy (VH) among demographic groups in the United Kingdom (UK) was an aversion to vaccinations' potential side effects, according to recent national research [10]. This conclusion was supported in the context of COVID-19 vaccinations, where fear of adverse effects was the most common reason for healthcare personnel and students in Poland declining to accept the vaccine [11,12]. As a result, a systematic evaluation of VH-fighting tactics found that increasing public awareness of vaccine effectiveness and transparency about side effects is critical for increasing vaccine uptake [13].
We are in a rapid infection spread caused by the virus (SARS-CoV-2) since it continuously mutates and spreads rapidly [14]. Twelve variants of the virus have already been seen as of now, the Delta and the latest Omicron [15] being considered the most contagious [16]. In this evolving situation, widespread immunization is critical to preventing the catastrophic COVID-19 pandemic. Therefore, the Bangladesh government started a vaccination program at the beginning of 2021 and approved seven vaccines for mass immunization in Bangladesh. They are Covishield (Oxford/ AstraZeneca), Pfizer/BioNTech (BNT162b2), Moderna (mRNA-1273), Johson & Johnson (Ad26.COV2.S), Sinopharm (BBIBP-CorV), Sinovac (CoronaVac), and Sputnik-V (Gamaleya) [17].
Bangladesh is a highly-populated country, and most of the people live in rural areas where misinformation and rumors are common. Hence, widespread ignorance, misinformation, and a lack of understanding concerning COVID-19 vaccines have persisted among the general population in Bangladesh since the start of the COVID-19 pandemic [18]. A significant VH has been found in Bangladesh per a cross-sectional study conducted in February 2021. According to the study, among people willing to take a COVID-19 vaccine (61%), only 35% were willing to take a vaccine immediately if available [4]. The main reason for the unwillingness was doubts regarding the vaccines' safety and efficacy [4]. As of December 11, 2021, only 25% of Bangladesh's 160 million people have been fully vaccinated [19]. Vaccine hesitancy might play a vital role in low vaccine uptake in Bangladesh. Until now, most of the data on COVID-19 vaccine safety and efficacy have been published in manufacturer-funded trials that adhere to regulatory criteria and are monitored by third parties [20]. A lack of independent studies on vaccine safety may have a detrimental effect on vaccine acceptance, which must be intensified to combat the spread of the virus. A few studies have already examined a specific vaccine's side effects. However, no studies have been found in the literature that examined most of the approved COVID-19 vaccines' side effects. Here, side effects refer to any common or severe effects such as pain and redness/swelling at the injection site, fever, headache, etc., that occur after taking a COVID-19 vaccine.
The objectives of this study were to inspect the side effects of the circulated COVID-19 vaccines in Bangladesh, identify potential risk factors of the vaccine side effects, and explore the perceptions about COVID-19 and its vaccines among general people in Bangladesh.

Study design
The study is based on a cross-sectional anonymous online survey conducted across Bangladesh from December 2 to December 26, 2021, and sought to shine a light upon the prevalence of the side effects of a range of COVID-19 vaccines on the Bangladeshi population. Participants in this survey had to be at least 12 years old and take at least one dose of a COVID-19 vaccine in Bangladesh. A link to an online survey (SurveyCTO) was shared on social media (FB, Messenger, WhatsApp, and Email). Authors' social media connection databases were used to share the survey link, and the recipients were also requested to share the link with their connections. At the outset, a section described the study's aim, the questionnaire's concept, assurances regarding respondents' confidentiality, and the study's voluntary nature. Additionally, it was indicated that participants could omit any question if it appeared to be sensitive. The online survey began with the respondents' informed consent and eligibility verification. The surveys for the participants aged < 18 years were conducted by their parents/ adult guardians. After completing the survey, participants were also asked to share the survey link with their connections. The study questionnaire was prepared in English (see online supplemental questionnaire) and then translated into Bangla. Several experts and pilot surveys were used to validate the questionnaire.

Sample size
A previous study [14] shows that 57% of general people had experienced the side effects of the COVID-19 vaccine. So then, the required minimum sample size is 501 calculated using the formula SS=(Z 2 *P(1-P)/a 2 )*def*NR where Z = 1.96 at 95% confidence level, prevalence (P = 0.5) of side effects of COVID-19 vaccines, the margin of error (a = 0.03); design effect (def = 1.6) for sampling variation; social media response rate from a previous study 70% [21].

Instruments
The study questionnaire was developed through an extensive literature review of similar studies with an eye on the context of Bangladesh. The survey comprised of questions regarding (i) Demographics (ii) COVID-19 Vaccination(s) Taken (iii) Underlying Health Conditions (iv) Side Effects of COVID-19 Vaccines (v) Knowledge of and Attitudes towards COVID-19 and its Vaccines. A panel of six experts with expertise in COVID-19 research and survey design was formed to review the questionnaire draft and assess its content validity. With ratings from the six experts, we computed a mean content validity index for items (I-CVI) of 0.946. According to Polit and Beck, with ratings from six or more experts, a mean I-CVI>=0.78 is considered good [22]. To estimate the instrument's internal consistency, we used Chronbach's Alpha statistic, and we found an Alpha score of 0.71, which is acceptable [23].

Consent and Ethical considerations
The study leads with explicit declarations of anonymity by design, objectives, and voluntary nature. Participants could skip any questions if they found one uncomfortable to answer. The study was approved by the Ethical Review Committee, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore-7408, Bangladesh (Ref: ERC/FBST/ JUST/2022-97).

Statistical analysis
The exploratory analysis (bivariate analysis, frequencies analysis, means, graphs, etc.) was conducted to inspect the raw data. The Chi-square test was performed to determine the correlation between demographic factors and vaccines' side effects. The multivariate logistic regression was used to identify the responsible factors for the intensity of the vaccines' side effects among general people. The covariates that showed statistically significant association with vaccine side effects at a 20% level of significance in the Chi-square test were included in the logistic regression model. We used Statistical software Stata (version 16) and R (version 4.1.2) to analyze and create graphs.

Patient and public involvement
This study did not include any patients. It was an online-based, voluntary, and anonymous study that collected data from general people aged 12 years or over who took at least one dose of a COVID-19 vaccine in Bangladesh. A comprehensive consent statement was included at the beginning of the survey describing the study's objectives, nature, types of questions to be asked, skipping options, etc. The consent also assured that the data would be used in a combined form only for research purposes.

Results
Background characteristics and vaccine prevalence Table 1 describes the background characteristics of the 1,180 survey responders. The respondents tended to be male (63.89%) and over the age of 50 (65.40%). Most respondents indicated that they were married (65.40%). Respondents were evenly split between urban (47.14%) and rural (52.86%) regions. The majority of respondents indicated having received the Sinopharm vaccine (66.50%), followed by Oxford/AstraZeneca (10.69%), Moderna (7.66%), and Pfizer-BioNTech (7.32%). However, only 1.60% of respondents received the Sinovac vaccine, and the remaining 6.23% did not know the name of the vaccine they had received. The Sinopharm vaccine was also distinctly more prevalent in rural areas than in urban Bangladesh. OxfordAstraZeneca, Pfizer-BioNTech, and Moderna vaccinations were mainly reported by respondents in urban areas Fig. 1.

Distribution of COVID-19 vaccines' side effects and their severity
Overall, 39.48% of the participants experienced at least one side effect after receiving a COVID-19 vaccine in Bangladesh (Fig. 3). The highest percentage (80.46%) of side effects were observed among people who received the Pfizer-BioNTech vaccine, and the second-highest prevalence of side effects (76.63%) was found among people who received Moderna, followed by 67.72% among people who took OxfordAstraZeneca vaccines (see Fig. 4). The lowest percentage of side effects was found among people who received Sinopharm (28%0.23) and Sinovac (21.05%) vaccines. Table 2 shows that among respondents who faced side effects from taking the OxfordAstraZeneca vaccine, 86% of them had to take medicines. Most of them suffered from injection site pain (96.51%), fever (94.19%), headache (81.40%), and redness/swelling at the injection site (79%). Very few of them slept less (14.29%) and were anxious (3.49%). A large proportion of the respondents who took the Pfizer vaccine suffered from injection site pain (90%), fever (80%), and headache (74.29%). Likewise, among those who received the Moderna vaccine, 97%, 91%, and 68.29% of participants suffered from injection site pain, fever, and headache, respectively. More than 70% of the respondents who faced side effects for Pfizer and Moderna vaccines, took medicines. In contrast, only 9.87% of people had to take medicine who received Sinopharm vaccines and faced side effects. Moreover, around 50% to 70% of respondents who took the Sinovac vaccine mentioned having injection site pain, fever, or headache. Fig. 5 shows the distribu-tion of symptoms lasting duration (in terms of the number of days) across different COVID-19 vaccines. Psychological issues like less sleep and anxiety were more prevalent among those who took the OxfordAstraZeneca vaccine. However, symptom durations were considerably short for those who received Sinopherm and Sinovac vaccines.

Factors associated with COVID-19 vaccine side effects
The multivariate logistic regression seeks to identify influential factors for experiencing the COVID-19 vaccine's side effects. It is based on those factors which have a significant association with experiencing side effects at a 20% level of significance (see Table 2). The estimated parameters from logistic regression generally have been interpreted in terms of the odds ratio. The odds are defined as the probability of experiencing the event divided by the probability of not experiencing the event [24,25]. The odds ratios presented in Table 3 with a 95% confidence interval indicate the odds of experiencing side effects in one particular group compared to the odds of experiencing side effects in the reference group. The parameters are considered statistically significant at a 5% level of significance. Table 4 displays the results of the logistic regression model. Vaccine side effects were significantly associated with types of COVID-19 vaccine. For example, the odds of having COVID-19 vaccine side effects among people who took the OxfordAstraZeneca vaccine were 4.51 times (95% CI: 2.53-8.04) higher than people who took the Sinopharm vaccine. Pfizer-BioNTech receivers showed 5.37 times (95% CI: 2.57-11.22) higher odds of side effects than Sinopharm receivers. Likewise, respondents vaccinated with Moderna experienced 4.28 times (95% CI: 2.28-8.05) higher side effects than those who took the Sinopharm vaccine.
Smokers were 3.6 times (95% IC: 2.30-5.62) more likely to suffer from side effects than non-smoker respondents. Respondents who took illicit substances were 1.46 (0.61-3.48) times more likely to experience the COVID-19 vaccine's side effects than those who did not (not statistically significant at 5% level). For underlying

Perception and attitude towards COVID-19 and vaccination
Perception and attitudes towards COVID-19 and vaccinations are shown in Table 5. Most respondents either agreed that vaccines check against serious illness (50.59%) or remained neutral (42.09%). In addition, a majority agreed that all eligible people should take COVID-19 vaccines (72.14%) and maintain safety protocols even after vaccination (85.02%). Moreover, 77.78% of people agreed that the government and policymakers should make it mandatory for all eligible people to receive a COVID-19 vaccine.
A considerable hesitancy was observed among the participants in allowing their children (5 years or older) to receive a COVID-19 vaccine. Only 25.59% of the respondents were extremely likely to let their children receive a COVID-19 vaccine when available to them. Furthermore, only 40.57% of the participants were found extremely likely to allow their older people (70 years or over) to take a COVID-19 vaccine. Most respondents chose not to take a stance on the likelihood of COVID-19 spreading across Bangladesh again (67.85%).

Discussion
The study investigated the side effects of all the COVID-19 vaccines being deployed in Bangladesh. About two-thirds of the 1,180 participants were males, and two-thirds were aged 50 years or older. Our study participants are relatively older, probably because COVID-19 vaccines were offered to older people on a priority basis in Bangladesh. However, there was almost a perfect balance in the proportions of urban and rural participants. The majority of the participants received the Sinopharm vaccine (66.5%).
The study revealed that less than half of the participants (39.48%) experienced at least one side effect after receiving a COVID-19 vaccine in Bangladesh (Fig. 3). The side effects reported were regular and mild. The most-reported side effects were injection-site pain, fever, headache, redness/swelling at the injection site, and lethargy ( Table 2). The side effects existed on an average of 1-3 days only, and no instance of serious effects/ hospitalization was found among the study participants. These findings are consistent with similar studies conducted in the Czech Republic, India, and Saudi Arabia [20,26,27], although the study conducted in India reported a somewhat higher prevalence of side effects.
Side effects were more prevalent among those who received Pfizer-BioNTech and Moderna vaccines (about 80%), followed by the OxfordAstraZeneca vaccine (Fig. 4). In contrast, the prevalence of side effects was substantially lower among those who received China-based Sinopharm and Sinovac vaccines (21%-28%). A study among health professionals in Slovakia found that after taking the mRNA-based COVID-19 vaccine, BNT162b2 (Pfizer), the great majority (91.6%) of Slovak health professionals experienced at least one side effect, which is persistent in our study. Furthermore, more than 70% of those who experienced side effects from Pfizer and Moderna vaccines had to take medication. In contrast, only onetenth of those who received the Sinopharm vaccine and experienced side effects had to take medication. The findings imply that mRNA-based Moderna and Pfizer vaccines cause stronger side effects than other vaccines.
The current study found a significant association between side effects and type of vaccines using the Sinopharm vaccine as the reference vaccine to compare. OxfordAstraZeneca, Pfizer-BioNTech, and Moderna vaccines showed respectively 4.51 times (95% CI: 2.53-8.04), 5.37 times (95% CI: 2.57-11.22), and 4.28 times (95% CI: 2.28-8.05) higher likelihood of causing side effects compared   to the Sinopharm vaccine (Table 4). Besides, women were less likely to report side effects following vaccination than their male counterparts. This is a mixed finding, with most studies reporting higher side effects among males [25][26][27][28][29] and others reporting the opposite [28]. Moreover, older people (greater than50 years) were more likely to report vaccine side effects than the younger ones, which also disagrees with most other studies [20,26,29]. The prevalence of side effects among rural participants was considerably lower than the urban participants. This might be attributed to the fact that most rural people received the Sinopharm vaccine, and we found that side effects were rare among those who received the Sinopharm vaccine.
Smokers exhibited a 3.6 times (95% CI: 2.30-5.62) higher likelihood of reporting side effects than non-smokers. In addition, those who had underlying health conditions (low blood pressure, severe allergic problems, chronic respiratory diseases, and anemia) showed a 3-4 times higher prevalence of side effects. Riad et al. (2021), in their study conducted among Slovak healthcare workers, also found a higher prevalence of side effects among people with underlying health conditions. However, the severity of side effects experienced by the people with underlying medical conditions was not any different in our study. Hence, people with underlying medical conditions should not hesitate to take a COVID-19 vaccine. Instead, they should take it immediately since they are at a higher risk for COVID-19 [30].
A lack of confidence about the efficacy of the vaccines was observed among participants (Table 5). Only half of the respondents agreed with the statement ''COVID-19 vaccines can protect you from serious COVID-19 illness (needing hospitalization, oxygen, ventilators, or death)"; others remained neutral or disagreed. Also, considerable hesitancy was found among the respondents in allowing children and older people to take a COVID-19 vaccine. Only one-fourth of the participants were ready to let their kids (five years or over) receive COVID-19 vaccines, while less than half of them were willing to allow their senior citizens (70 years or over). These findings are consistent with a survey conducted in the USA in October 2021. Only about one-third of parents of children aged 5 to 11 years (27%) were ready to acquire a vaccine for their younger child as soon as one is approved, while a third said they would wait to see how the vaccine worked [31].
Vaccines' successes cannot be determined by only their side effects. A higher prevalence of minor side effects does not imply that a vaccine is inferior in function to another vaccine with a lower prevalence of side effects. The possibility of minor side effects following COVID-19 vaccination can be viewed positively: as a necessary precursor to a successful immunological response [32]. Vaccine side effects are almost always moderate and temporary, indicating that the vaccine is accomplishing its purpose of increasing IFN production, the body's natural immune stimulant [32]. This study and many other studies conducted across the world found COVID-19 vaccines' side effects are regular and temporary [20,[33][34][35][36][37][38][39][40]. Also, it is proven that COVID-19 vaccines effectively prevent serious COVID-19 illnesses (needing hospitalization, oxygen, ventilators, or death) [41]. Therefore, vaccines are the most powerful weapon available to us in the fight against the everpervasive COVID-19 pandemic.

Strengths and limitations of the study
To the best of the authors' knowledge, this study is the first to investigate the potential side effects of several (five) COVID-19 vaccines in Bangladesh. In addition, the study identified influential factors for experiencing side effects and their severity among the general people of Bangladesh. Furthermore, participants of this study were the general people. Most of the previous studies of this nature were conducted among healthcare workers only.
However, there are some limitations to this study. First, due to convenience sampling selection approaches that were part of the online survey approach, there might be some selection biases, such as fewer low education or illiterate participants. Second, since the  study was online, voluntary, and self-administered, we cannot confirm the seriousness of all participants while filling out the questionnaire causing potential information bias.

Conclusion
Like many other studies and clinical trial results, this study found that COVID-19 vaccines are safe. The most reported side effects found in this study were injection-site pain, fever, headache, redness/swelling at the injection site, and lethargy which were mild/regular and lasted 1-3 days. Prevalence of side effects differed by vaccine type with China-based vaccines showing the least prevalence of side effects. Males, older (greater than50 years), urban people, smokers, and people with underlying health conditions exhibited a significantly higher likelihood of reporting side effects after receiving COVID-19 vaccines. A lack of confidence in vaccines' efficacy and a substantial level of hesitancy in allowing children (age five years or over) and senior citizens (70 years or over) to receive COVID-19 vaccines were observed.
Misconceptions about the COVID-19 vaccine's safety and efficacy may influence people's opinions and decisions, adding to a self-perpetuating cycle of negative news. As a result, all responsible parties should combat misinformation by vigorously sharing true information about the vaccination's risks and benefits. The findings of this study will help counter misinformation about the safety of COVID-19 vaccines and thus combat vaccine hesitancy, particularly in Bangladesh and other lower-income countries.
This study investigated short-term/immediate side effects generated from receiving COVID-19 vaccines. However, the long-term side effects are yet to be explored. Future research should focus on the long-term side effects of the COVID-19 vaccines.
Author Contributions All the authors contributed significantly to the preparation of the final manuscript. MM and SM conceptualized and designed the study. MM and SM also developed the instrument with input and feedback from all other authors. AUM, PH, AM, MTA, FFA, AI, and MMR helped with data collection and supervision, data cleaning, writing, and proofreading. SM was also responsible for data analysis. In addition, MM and SM wrote the first draft of the manuscript. MSR, HRK, and MI supervised the entire study (continuous feedback, editing, proofreading, etc.). The order of the authors' list indicates the level of contribution for each author in the entire study.

Data availability
I have attached data link.

Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.