A large-scale prospective study on COVID-19 vaccine preferences, anxiety, and post-vaccination adverse outcomes in Turkiye

Authors

Abstract

Aim The declaration of the COVID-19 pandemic has caused many people around the world to hesitate to get the COVID-19 vaccine due to its safety and possible side effects. This study aimed to investigate the relationship between the tendency to prefer inactivated or mRNA-based COVID-19 vaccines, the incidence of side effects due to chronic diseases, and pre-vaccination anxiety levels.
Methods This is a prospective cohort study conducted in a single center. 6292 individuals over the age of 18 who applied to the COVID-19 vaccination unit of a university hospital in Türkiye were included. Participants were administered a questionnaire asking about vaccine preference, COVID-19 history, pre-vaccination anxiety level, and presence of chronic diseases. Participants were contacted seven days after vaccination and asked about side effects.
Results The group that preferred mRNA-based vaccines consisted of younger and working individuals on average, while those who preferred inactivated vaccines were older and had more chronic diseases (p<0.001). In participants with chronic diseases who received mRNA-based vaccines, the rate of reporting mild to moderate adverse events was high, but serious adverse events were rare; no serious adverse events were seen in the chronic disease group who received an inactivated vaccine. Similar to the first dose, the frequency of side effects was significantly higher in participants who reported ‘I feel good’ with the mRNA-based vaccine than with the inactivated vaccine (p<0.001).
Conclusion Providing more counseling and support to individuals with high anxiety levels about vaccine safety before vaccination can help reduce the possible side effects experienced.

Keywords

Introduction

The mRNA-based COVID-19 vaccine (Biontech) was the first COVID-19 vaccine approved for emergency use by the World Health Organization (WHO) on December 31, 2020, and was first administered on August 23, 2021. However, the inactivated COVID-19 vaccine (Sinovac) was approved for emergency use by the WHO on June 1, 2021. The short time between the declaration of the pandemic and the development of the first approved vaccine caused many people to hesitate to get vaccinated due to concerns about its safety and possible side effects ⁶. The COVID-19 pandemic has caused major disruptions, including death, economic instability, and social isolation, contributing to a global increase in mental health problems such as anxiety, depression, and fear. Additionally, media narratives and conflicting information regarding vaccine efficacy and safety have fueled public uncertainty and vaccine hesitancy [7–9]. This study aimed to determine the demographic characteristics of individuals who preferred Biontech and Sinovac vaccines, assess the impact of chronic diseases on side effect incidence, and examine the relationship between pre-vaccination anxiety and post-vaccination adverse effects.
To our knowledge, few large-scale empirical studies have directly examined how pre-vaccine anxiety levels influence the perception or reporting of vaccine-related side effects. This study fills that gap by exploring the interaction between psychological factors and adverse event reporting in a real-world vaccination context.

Materials and Methods

Study design and populationThe study is a prospective cohort study conducted at a university hospital in Türkiye between October 2021 and March 2022. Written informed consent was obtained from those who volunteered to participate. Participants then selected the vaccine they wanted to receive (Biontech-Sinovac). Participants were contacted by phone seven days after vaccination. This follow-up period was chosen based on existing literature and clinical guidelines that indicate most vaccine-related adverse events occur within the first 7 days post-vaccination. Four nurses from the Selçuk University COVID-19 vaccination center, who received training on the study, administered a questionnaire to patients asking if they experienced any side effects after vaccination. Of the 7325 individuals who applied to the vaccination center, 6292 were included in the study according to the inclusion criteria. Participants with incomplete data were excluded using listwise deletion. No imputation techniques were applied. Although a formal a priori power analysis was not conducted, the large sample size provided sufficient statistical power for subgroup comparisons and ensured reliable estimation of adverse event rates. The study’s inclusion criteria were volunteers aged 18 and over who had not previously received any COVID-19 vaccine and agreed to participate in the study. Those who had previously received another COVID-19 vaccine, those with uncontrolled chronic diseases, those under the age of 18, and those who were not volunteers were excluded from the study.It was confirmed that all aims and instruments of the study were designed in accordance with the ethical standards of the institutional research committee, the Declaration of Helsinki, and its subsequent amendments.
Data collection instrumentsResearchers developed a questionnaire that asked participants about their sociodemographic characteristics. Participants rated their pre-vaccine anxiety level on a scale of 0 to 5 (0: I feel very bad, 1: bad, 2: neither good nor bad, 3: normal, 4: good, 5: excellent). For ease of analysis, these statements were divided into three categories: 0–1 (I feel bad), 2–3 (I feel normal), and 4–5 (I feel good). Although this scale provided a quick ordinal assessment suitable for field application, it is not a validated psychometric instrument. Future studies may consider using standardized measures such as the Generalized Anxiety Disorder Scale (GAD-7) or Visual Analog Scale (VAS-Anxiety). Internal consistency analysis (e.g., Cronbach’s α) was not performed and represents a limitation of this study.
Side effect classification
Mild side effects included: redness, fever, swelling, and pain at the injection site. Moderate side effects included: fatigue, headache, arthritis, vertigo, myalgia, arthralgia, appetite changes, taste and smell disturbances, diarrhea, abdominal pain, fever, nausea, runny nose, sore throat, lymphadenopathy, cough, and pruritus. Serious side effects included: chest pain, dyspnea, hypotension and hypertension, and anaphylaxis [10–12].
Statistical analysisThe study data were transferred to a computer. The Mann-Whitney test was used to compare vaccines by age. Cross-tabulations were created for comparisons of vaccines, doses, side effects, and anxiety levels. MS-Excel 2010 and IBM SPSS Statistics 22.0 were used for statistical analysis and calculations. A p<0.05 was considered significant for statistical analysis.
Ethical approvalThis study was approved by the Selcuk University Local Ethics Committee (Date: 2021-09-28, No: 2021/434).

Results

Our study was conducted on 6292 volunteers. Of the volunteers, 4292 (68.2%) completed 2 doses of Biontech, and 2000 (31.8%) received the Sinovac vaccine. The median age of the volunteers was 54.0 (IQR=32.0) years, 52.1% were female, and 47.9% were male. The mean age of the Sinovac group was higher than the Biontech group (p<0.001, 95% CI: 3.22–4.78). Married participants preferred Sinovac more (p<0.001, 95% CI: 2.88 – 3.62). Smoking and alcohol consumption rates were higher in the Biontech group (p<0.001, 95% CI: 2.32 – 3.22). Sinovac was more preferred among employed participants (p<0.001, 95% CI: 1.91 – 2.42).
The education level of the Sinovac group was significantly lower than the Biontech group (p<0.001, 95% CI: 5.44 – 6.87). Among participants with a history of allergies (9.5%), the rate of those who preferred Biontech was significantly higher than those who preferred Sinovac (p<0.001). 1101 (17.5%) of the participants had COVID-19 before being vaccinated. Among participants with a history of COVID-19, 17.9% of those who preferred Biontech were 16.6%, while this rate was 1336 (21.2%) of the participants had at least one chronic disease. The most common chronic diseases were hypertension (n=780, 58.4%), heart diseases (n=190, 14.2%), and asthma (n=184, 13.8%). 800 (18.6%) of the participants who preferred Biontech and 536 (26.8%) of those who preferred Sinovac had at least one chronic disease. Among the participants who had at least one chronic disease, the rate of those who preferred Sinovac was significantly higher than those who preferred Biontech (p<0.001). Among patients with both hypertension, hyperthyroidism, and COPD, the rate of those who preferred Sinovac was significantly higher than those who preferred Biontech (p<0.001). Among patients with both diabetes mellitus and asthma, the rate of those who preferred Biontech was significantly higher than those who preferred Sinovac (p<0.001). shown in Figure 1. No side effects, such as changes in blood pressure or chest pain/shortness of breath, were observed in the Sinovac group.Side effects were observed in 403 (6.4%) participants after the first dose, while 419 (6.7%) participants experienced side effects after the second dose. The frequency of side effects was significantly higher in the Biontech group at both doses (p<0.05).Serious side effects were defined as events such as chest pain, shortness of breath, hypotension, or hypertension requiring medical attention, or anaphylaxis. No serious side effects were observed in any of the participants after either dose of Sinovac. Serious side effects were observed in 1.3% of participants after the first dose of Biontech and in 1.1% of participants after the second dose. In the Biontech group, 22 of the 56 participants (39.3%) who experienced serious side effects after the first dose also experienced serious side effects after the second dose. Of the 232 participants (10.8%) who experienced mild to moderate side effects after the first dose of Biontech, 25 also experienced serious side effects after the second dose (Table 1).The frequency of side effects in patients with chronic diseases by dose is shown in Table 2. After the first dose of Biontech, the frequency of side effects in participants with chronic diseases (13.5%) was significantly higher than in participants without chronic diseases (5.2%) (p<0.001). After the second dose of Biontech, the frequency of side effects in participants with chronic diseases (13.8%) was significantly higher than in participants without chronic diseases (5.5%) (p<0.001).Mild-to-moderate side effects were observed in 10.6% of participants who received Biontech, compared to 5.6% in those who received Sinovac. The frequency of side effects was significantly higher in Biontec than in Sinovac (p=0.001).
Of all participants, 730 (11.6%) said they felt bad-terrible at the moment, while 1929 (30.7%) said they felt good-excellent. As a result of the combination, it was found that the anxiety level differed according to the vaccine (p<0.001). Participants who said ‘I feel normal’ were removed from the analysis to determine which vaccine or anxiety level caused the difference. Participants who said ‘I feel bad’ and ‘I feel good’ were compared with the vaccine. Participants who said ‘I feel bad’ were considered to have high levels of anxiety, while those who said ‘I feel good’ were considered to have low levels of anxiety. It was determined that the rate of those who said ‘I feel bad’ in participants who would receive Biontech was significantly higher than in participants who would receive Sinovac, while the rate of ‘I feel good’ was higher in participants who would receive Sinovac (p<0.001). At this stage, all participants who experienced any side effects were coded as ‘There is a side effect’, and the others were coded as ‘No side effect’. Anxiety levels and incidence of side effects by vaccine are summarized in Table 3. The proportion of participants reporting ‘I feel bad’ (12.9%) was higher than that of those receiving Sinovac (8.8%) (p<0.001). The proportions reporting ‘Neutral’ and ‘I feel good’ were very similar for both Biontech and Sinovac. In participants who reported poor anxiety, the rates of side effects after each dose of Biontech were lower than in the Sinovac group (for both doses; p<0.001). In participants who reported neutral anxiety, the rates of side effects after each dose of Biontech were higher than in the Sinovac group (for both doses; p<0.001). In participants who reported good anxiety, the rates of side effects after each dose of Biontech were higher than in the Sinovac group (for both doses; p<0.001). In participants who reported low anxiety, the incidence of side effects was significantly higher with Sinovac compared to Biontech after every second dose (p<0.001). Similar to the first dose, the incidence of side effects was significantly higher with Biontech compared to Sinovac in participants who reported “I feel well” (p<0.001). Among participants who did not feel well, the incidence of side effects after the second dose was significantly higher with Sinovac compared to Biontech (p<0.001).In summary, our findings show that Biontech recipients, who were generally younger and healthier, reported a higher frequency of mild-to-moderate side effects compared to Sinovac recipients. Chronic illness increased the rate of adverse events only among Biontech recipients. Additionally, individuals with high pre-vaccine anxiety levels reported more side effects in the Sinovac group, while this pattern was not observed in the Biontech group. These results highlight the complex interaction between vaccine type, chronic conditions, and psychological state in shaping post-vaccination experiences.

Discussion

Vaccine choice and demographicsThe average age of those who preferred Sinovac was higher than Biontech. The prevalence of conditions such as hypertension and COPD increases with age, while conditions such as asthma and diabetes can occur independently of age ¹³. In our study, individuals with conditions such as hypertension and COPD mostly preferred Sinovac, while those with conditions such as diabetes and asthma mostly preferred Biontech. This may be due to the Ministry of Health’s prioritization of those aged 65 and older in its vaccination program, and Sinovac being the first COVID-19 vaccine in Türkiye ¹⁴.
A 2021 study showed that the severity and frequency of side effects are related to the vaccine type ¹⁵. In our study, consistent with the literature, a higher rate of non-life-threatening mild-to-moderate side effects was detected in both the Biontech and Sinovac groups ^16,17,18. While the incidence of post-vaccination anaphylaxis is very low for many vaccines, the incidence of post-vaccination anaphylaxis is slightly higher for the Biontech group ¹⁹. In our study, no serious side effects, including anaphylaxis, were observed in the Sinovac group. Although serious side effects were observed in the Biontech group, no anaphylaxis was observed.In our study, more side effects were observed in the Biontech group, which had a lower average age. A Polish study found an increased risk of systemic side effects in younger individuals ²². Another study found a higher incidence of side effects after vaccination in younger individuals ¹³. This may be explained by the stronger immune response induced by the vaccine in younger individuals ²³.
Chronic illness and side effectsThere are studies in the literature showing both an increase in the frequency and risk of adverse events following vaccination in individuals with chronic diseases, a nonincrease, and a decrease ^13,24. Our results in the Biontech group support the literature suggesting an increased risk of adverse events in individuals with chronic diseases. However, our results in the Sinovac group support the literature suggesting that the presence of chronic diseases does not influence the increase in the frequency of adverse events. This difference is thought to be due to the different techniques used in vaccine production, such as inactivated and mRNA.Hypertension, commonly seen in older populations, was also the most prevalent chronic condition in our sample ²⁵. This aligns with existing literature and may partially explain the vaccine preference patterns observed. Similar to the literature, our study found a higher prevalence of hypertension, COPD, and thyroid disease in the Sinovac group, where the mean age was higher. Diabetes and heart disease, which are expected to increase with age, were observed at higher rates in the Biontech group, where the mean age was lower. This may be due to the tendency of younger chronic patients to prefer mRNA vaccines. Chronic disease has been reported to increase the frequency of side effects only with viral vector-based COVID-19 vaccines and does not affect the risk of side effects with mRNA-based vaccines ²².Studies with different doses of Sinovac have shown that side effects are mild, even at high doses ¹¹. A study comparing the side effects of Sinovac and Biontech noted fewer side effects in the Sinovac group and a significant difference in the frequency of side effects between doses ²⁴. In our study, the Biontech group experienced a higher rate of side effects at both doses. In the study by Riad et al., individuals who received two doses experienced more side effects than those who received one dose ²⁴. In our study, no significant difference was found in the side effects observed after the first and second doses in either group. However, the FDA reported that 10.8% of participants receiving Biontech experienced mild side effects after the first dose and serious side effects after the second dose ²⁶. In our study, systemic and local side effects of Biontech were more common with the second dose than with the first dose.
Anxiety and symptom perceptionIn one study, 25% of participants stated that they avoided the vaccine due to possible side effects ¹². In a study of those vaccinated with Sinovac, higher rates of side effects were reported in individuals who were concerned about side effects ²⁷. In our study, the frequency of side effects was lower in the Biontech group reporting high anxiety. The frequency of side effects was higher in neutral or no-anxiety participants in the Biontech group. While lower rates of side effects were reported in the Sinovac group in the literature, the frequency of side effects was higher in participants with high anxiety. This suggests that pre-vaccine anxiety may increase the frequency of side effects. There are limited studies evaluating the frequency of side effects in individuals anxious about receiving the COVID-19 vaccine.
Since the study was conducted at a single center, the findings might reflect regional characteristics; however, the large sample size still provides a robust data set.

Limitations

Single-center, not including individuals under the age of 18, starting the vaccination program in Türkiye by administering the Sinovac vaccine to individuals over the age of 65, not asking about anxiety levels after vaccination.

Conclusion

Our study evaluated factors influencing COVID-19 vaccine preference and post-vaccine experiences in a large cohort. We found that demographic factors and pre-vaccine anxiety levels can influence vaccine choice and perceived side effects. These findings highlight the need for strategic communication by healthcare providers: family physicians play a critical role in informing the public and addressing vaccine hesitancy.
Our study aims to prevent negative thoughts among vaccine-hesitant individuals and reduce anxiety by informing vaccine avoidants.
Our study is one of the few studies to evaluate the relationship between pre-vaccine anxiety and side effect outcomes, filling an important gap in the literature.

Declarations

References

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About This Article

Received:

July 4, 2025

Accepted:

August 11, 2025

Published Online:

August 21, 2025