We conducted the National Stroke Screening Survey on people over 40 years old in a rural village and a urban community in Linhai City, China, to obtain information about risk factors of cardiovascular and cerebrovascular diseases (19). The two areas were chosen according to the proportion to the local population size and geographical locations. Meanwhile, adverse reactions to the COVID-19 vaccine were investigated. The cluster sampling method was used and all residents aged ≥40 years in both two areas were surveyed. The survey was conducted face-to-face at the appointed time by trained investigators, and the participants were asked to answer the questions on the questionnaires. The investigators recorded the answers in the questionnaire, imported the data into MS Excel. The investigators had the same background of cerebrovascular disease. They had been trained on knowledge of COVID-19 vaccine and the standardized procedures, and passed the training examination. Professional quality control personnel supervised the conduction of the research. The survey was conducted between 3 June 2021 and 18 September 2021.

The questionnaire was divided into two parts as follows: The investigation of risk factors related to stroke and adverse reactions to the vaccine. The survey of risk factors related to stroke was based on questionnaire of China National Stroke Screening and Prevention Project (20), which included basic demographic information (such as age, sex, education level, occupation, and marital status), lifestyle (e.g., smoking, drinking, exercise, and dietary habits), major medical history (heart disease, hypertension, diabetes, dyslipidemia, etc.), and family history. At the same time, physical examination, ECG examination, and laboratory examination of blood sugar and blood lipids were performed. Laboratory examination results were also imported into MS Excel and used to diagnose emerging diseases, such as heart disease, hypertension, diabetes, and dyslipidemia.

The eight risk factors for stroke included high blood pressure, dyslipidemia, diabetes, smoking, atrial fibrillation or valvular heart disease, obesity, lack of exercise, and family history of stroke. According to the stroke risk scorecard recommended by the Stroke Prevention and Control Engineering Committee of the National Health and Family Planning Commission (21), the population was divided into low-, medium-, and high-risk groups: people with three or more of the above factors or a history of stroke or transient ischemic attack (TIA) were considered to have a high stroke risk. People with one of the three factors (hypertension, diabetes, and atrial fibrillation) were considered to have a medium stroke risk. The rest were considered to have a low stroke risk.

The questionnaire on adverse reactions was based on the vaccine manual and revised according to the advice of preventive experts, which included the following: (1) the producer of the used SARS-CoV-2 vaccine. In Linhai city, the vaccines that had been marketed and used were inactivated vaccines produced by Beijing SINOVAC LIFE Sciences Co., Ltd., Beijing Institute of Biological Products Co., Ltd., Wuhan Institute of Biological Products Co., Ltd., adenoviral vector vaccine produced by CanSino Biologics Inc., and recombinant subunit vaccine produced by Anhui Zhifei Longcom Biopharmaceutical Co., Ltd.; (2) allergy history; (3) the number of doses, local and systemic adverse reactions after each dose; (4) knowledge of vaccine being used (What type of SARS-CoV-2 vaccine were you injected?); (5) attitude toward the SARS-CoV-2 vaccine (“Will you take the SARS-CoV-2 vaccine for your family proactively?” and “Are you worried about the adverse reactions of the SARS-CoV-2 vaccine?”) (22); (6) whether existing diseases were aggravated after vaccination. The reasons for the non-vaccination of the unvaccinated population were also investigated. The questionnaire was included in the Supplementary material.

Categorical variables were expressed as proportions (%) and continuous variables were expressed as the mean ± standard deviation when the data conformed to the normal distribution or median (quartile) when non-normal distribution was observed. Univariate analysis via the χ² test was used to assess the potential factors associated with adverse reactions. Multinomial logistic regression was used to identify the factors associated with adverse reactions. Tests were two-sided, with significance set at P ≤ 0.05. Data analysis was performed using SPSS software (version 16.0, SPSS Inc.).

A total of 1,747 (74%, 1,747/2,374) community or village residents over the age of 40 completed the survey. Reasons for non-participation included subjective refusal after knowing the content of the survey, or lack of time to participate in the survey. Of the participants surveyed, 138 were unvaccinated, and 1,609 were vaccinated. Among the vaccinated participants, the age is 59.1 ± 9.5, 1,124 were female (69.9%). Marital status, education level, and occupation are presented in Table 1. Five hundred and ninety-two (36.8%) had a low risk of stroke, 355 (22.1%) had a medium risk of stroke, and 662 (41.1%) had a high risk of stroke. The frequency distribution of stroke risk factors (such as TIA, previous stroke history, hypertension, diabetes) is shown in Table 1. One thousand three hundred and twenty-four participants received the inactive vaccines, 11 received the adenoviral vector vaccine, and 20 received the recombinant subunit vaccine. The rest did not know the vaccine type they received. 81.3% of the participants knew the vaccine being used. 7.8% of the participants worried about adverse reactions to the vaccine, but 98.6% of participants would receive the vaccine for their family and friends. 4.8% had an allergy history (Table 1).

We analyzed the incidence of adverse reactions in people with a low, moderate, and high risk of stroke after the first and second injection. After the first injection, the incidence of adverse reactions was 18.2, 14.1, and 16.5% in people with low, medium, and high risk of stroke, respectively. The main types of adverse reactions were pain, fatigue at the injection site, and systemic muscle soreness, but there was no difference among the different grades of stroke risk (Table 2). After the second injection, the incidence of adverse reactions was 14.4, 13.7, and 13.3% in people with low, medium, and high risk of stroke, respectively. The main adverse reactions were pain, swelling or itching at the injection site, as well as fatigue, systemic muscle soreness, and rash. There was no difference among the different grades of risk after the second dose (Table 3). The non-solicited adverse reactions include abnormal menstruation, numbness of the limbs, insomnia and palpitations.

In addition, we investigated whether vaccination aggravated existing diseases, such as atrial fibrillation, hypertension, dyslipidemia, diabetes, stroke sequelae, and frequency of TIA attacks. The results showed that 3 people reported a slight increase in blood pressure, 1 reported a slight increase in blood lipid levels, and 3 reported a slight increase in blood sugar levels. In the vaccinated population, there was no increase in the frequency of TIA attacks and aggravation of stroke sequelae.

To identify the factors associated with adverse reactions, univariate analysis using the χ² test was carried out for participants who were double vaccinated. The factors included sex, age, marital status, education level, occupation, type of vaccine, risk level, previous TIA, previous stroke, family history of stroke, atrial fibrillation or valvular heart disease, hypertension, dyslipidemia, diabetes, smoking history, overweight or obesity, lack of exercise, knowledge of inactivated vaccine being used, worry about adverse reactions, proactive vaccination for the family, and sleep quality before vaccination. The results indicated that sex, age, education level, knowledge of inactivated virus being used, worry about adverse reactions, and sleep quality before vaccination were significantly associated with adverse reactions (Table 4).

Then, a multinomial logistic regression model was developed to identify the factors associated with adverse effects. Variables that were significant at P < 0.05 as a result of the univariate analyses were included. As shown in Table 5, sex [female vs. male, Odds Ratio (OR) = 1.90, 95% confidence interval (CI): 1.33–2.72], knowledge of inactivated vaccine being used (no vs. yes, OR = 1.67, 95% CI: 1.15–2.42), sleep quality before vaccination (good vs. poor, OR = 0.34, 95% CI: 0.18–0.62; moderate vs. poor, OR = 0.29, 95% CI: 0.15–0.55), worry of adverse reactions (no vs. yes, OR = 0.50, 95% CI: 0.27–0.94) were significantly associated with adverse reactions after one vaccination. In addition, age (40–50 vs. ≥70, OR = 1.60, 95% CI: 0.88–2.92), worry of adverse reactions (no vs. yes, OR = 0.12, 95% CI: 0.06–0.24), and sleep quality before vaccination (Good vs. poor, OR = 0.33, 95% CI: 0.13–0.81; moderate vs. poor, OR = 0.18, 95% CI: 0.07–0.47), education level (primary and below vs. college and above, OR = 0.28, 95% CI: 0.1–0.81) were significantly associated with adverse reactions after both vaccinations.

In this survey, 138 people were not vaccinated, of whom 120 (87.0%) were at medium or high risk of stroke. We investigated the reasons for not being vaccinated. The results showed that worry about the aggravation of the existing disease was the main cause, with a total of 63 people accounting for 64.9%. Other causes were fear of adverse reactions to the vaccine (17.5%), vaccination taboos (6.2%), and concern about interactions with drugs (5.2%) (Figure 1).