GRAPHICAL ABSTRACT

Key Message

• A nationwide self-controlled case series study investigated whether COVID-19 vaccination increases the risk of new-onset seizures (NOS) in adults by analyzing over 42 million vaccine recipients.

• The results showed no increased risk of NOS within 28 days after vaccination for most vaccine types, with the exception of a marginally elevated risk for the mRNA-1273 vaccine.

• Overall, the study found no evidence of increased NOS risk following COVID-19 vaccination, supporting the safety of these vaccines for clinical decision-making.

INTRODUCTION

Since the emergence of coronavirus disease 2019 (COVID-19), over 13.3 billion doses of COVID-19 vaccines have been administered worldwide [1]. The implementation of this mass vaccination campaign has been crucial not only for preventing COVID-19 infections but also for improving the long-term management of COVID-19-related disease [2-4]. Although COVID-19 vaccines are recognized as highly effective in preventing infection and its post-acute sequelae, numerous cases of new-onset seizures (NOS) following COVID-19 vaccination continue to be reported among diverse ethnicities, age groups, and vaccine types [5-12]. These ongoing reports undermine public trust in vaccines, highlighting the importance of evaluating the association between COVID-19 vaccines and NOS.

While the precise biological mechanisms behind vaccine-induced seizures remain unidentified, plausible explanations include immune-mediated abnormal neuronal activity [13] or seizures triggered by fever due to a sudden increase in body temperature [14]. Alternatively, seizures could occur secondary to other neurological adverse events, such as ischemic stroke, encephalitis, or cerebral venous sinus thrombosis following vaccination [8]. Given that COVID-19 infection itself is a known risk factor for seizures [15], well-designed studies are required to differentiate the effects of COVID-19 vaccination from those of infection to accurately assess the relationship with NOS. Previous observational studies addressing this clinical concern have either lacked sufficient statistical power due to small sample sizes or were limited to assessing only a few vaccine types [16-18].

To address this evidence gap, the current study aimed to assess the association between the risk of NOS and immunization against COVID-19 using a self-controlled case series (SCCS) analysis based on a nationwide Korean database that includes multiple COVID-19 vaccine types.

MATERIALS AND METHODS

Data source

This study was conducted as part of Korea’s COVID-19 Vaccine Safety Research Committee (CoVaSC), contributing to the generation of evidence supporting the safe use of COVID-19 vaccines. CoVaSC investigators use a large, linked database combining the COVID-19 vaccination registry (from February 26, 2021, to October 31, 2022), managed by the Korea Disease Control and Prevention Agency (KDCA), and healthcare claims data (from January 1, 2002, to October 31, 2022) provided by the National Health Insurance Service (NHIS) [19]. In Korea, vaccine distribution is government-managed, enabling KDCA to systematically collect vaccination records for the entire Korean population since the initiation of COVID-19 vaccinations (February 26, 2021). These records include vaccination dates, doses, and the specific vaccine types administered. The NHIS, serving as a single-payer insurer, covers the entire Korean population (>50 million people). Comprehensive healthcare utilization data, including medical diagnoses, drug prescriptions, and medical examinations, are anonymized via personal identifiers and made accessible to researchers. By linking claims data to the COVID-19 vaccination registry, a large-scale data source was established to identify adverse events among vaccine recipients. Diagnostic records are coded according to the International Classification of Diseases, 10th revision (ICD-10), and prescription drug information is identified using domestic drug chemical codes based on the Anatomical Therapeutic Chemical (ATC) classification of the World Health Organization.

Study population

We identified adults aged 18 years or older who received their first dose of the COVID-19 vaccine between February 26, 2021, and March 1, 2022. Among these, individuals diagnosed with seizures recorded as the primary diagnosis and prescribed anti-seizure medications (ASMs) between February 26, 2021, and October 31, 2022, were included. As the study employed a self-controlled case series design, only patients experiencing both the exposure and the outcome of interest within the predefined observation period were eligible for inclusion. We excluded participants who were foreigners, enrolled in clinical trials for COVID-19 vaccines, vaccinated abroad, or those with vaccination records deviating from the recommended COVID-19 vaccination guidelines (e.g., more than 1 vaccine type administered on the same day, or a record for the second dose without documentation of the first dose). Additionally, individuals diagnosed with seizures in the year prior to their first seizure diagnosis during the predefined observation period, and those prescribed ASMs within 180 days prior to the date of their first COVID-19 vaccination, were excluded to focus exclusively on incident cases. Patients diagnosed with seizures more than 240 days after the first vaccine dose were also excluded. The flowchart illustrating the selection process for study participants is presented in Figure 1.

Study design

We employed a SCCS design [20] to evaluate the risk of NOS following COVID-19 vaccination. This choice was motivated by the high COVID-19 vaccine exposure rates within the Korean population, which rendered it challenging to select appropriate controls receiving different vaccines. The SCCS design estimates the relative incidence between risk and control windows within the same individual. Since each individual serves as their own control, this design inherently minimizes confounding from time-invariant covariates, such as sex and genetic factors. As presented in Supplementary Material 1, the observation period was specified as 240 days following the first vaccine dose. Within this period, intervals up to 28 days after each vaccination dose were designated as risk windows, during which each individual is presumed to have a higher risk of the outcome due to vaccination. The 28-day risk window was chosen based on evidence from clinical trials indicating that neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peak at approximately 28 days post-vaccination [21,22]. The remaining observation periods outside these risk windows served as control windows.

Vaccination against coronavirus disease 2019

All identifiable doses (first, second, third, fourth) and types of COVID-19 vaccines administered were considered exposures. The following vaccine types were available in Korea during the study period: BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), mRNA-1273 (Moderna), Ad26.COV2.S (Janssen), and NVX-CoV2373 (Novavax). The recommended intervals for the primary series between the first and second doses were 28 days for mRNA-1273 and ChAdOx1 nCoV-19, and 21 days for BNT162b2 and NVX-CoV2373. A single dose of Ad26.COV2.S constituted a complete primary series. Individuals were categorized as receiving a homologous vaccine series if they received the same COVID-19 vaccine type for all doses, or heterologous if they received different vaccine types for any of the doses.

Outcome

The outcome of interest was NOS, defined as a seizure diagnosis recorded as the primary diagnosis in either inpatient or outpatient settings, accompanied by a prescription for ASMs on the same day. Seizure diagnoses were identified using ICD-10 codes (G40, G41, R56, F44.5), and ASM prescriptions were identified by ATC codes (N03A) (Supplementary Material 2). Recurrent seizures were not included as outcomes, and only the first seizure occurrence was considered to avoid violating the assumptions inherent to the SCCS design [20]. We observed all NOS events occurring during the predefined observation period among eligible participants, and calculated incidence rates within the designated risk and control windows.

Statistical analysis

Descriptive statistics were used to summarize NOS cases, categorized by whether they occurred within risk or control windows, according to baseline characteristics such as age, sex, residence, comorbidities, and vaccine doses or types administered. The t-test was conducted for continuous variables, and the chi-square test was utilized for categorical variables. A p-value of less than 0.05 was considered indicative of statistical significance. For the primary analysis, conditional Poisson regression models were used to estimate the number of events, person-years (PYs), incidence rate ratios (IRRs), and corresponding 95% confidence intervals (CIs) to evaluate the risk of NOS following vaccination. Secondary analyses included stratified evaluations by vaccine doses (first, second, third, fourth, or first/second combined), vaccination strategies (heterologous or homologous), and vaccine platforms (mRNA or non-mRNA).

We also conducted subgroup analyses stratified by age group (18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥80 years), sex (male, female), insurance type (health insurance, Medical Aid), residential area (metropolitan, rural), Charlson comorbidity index score (<5, ≥5), and history of specific comorbidities recorded during the year preceding the first vaccination dose. These comorbidities included myocardial infarction, congestive heart failure, peripheral vascular disease, stroke, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, mild liver disease, diabetes mellitus, diabetic complications, hemiplegia/paraplegia, renal disease, cancer, serious liver disease, solid or metastatic tumors, and human immunodeficiency virus infection.

Several sensitivity analyses were additionally performed. First, we repeated the main analysis using alternative risk windows (14 and 42 days) to evaluate how different timeframes influenced NOS risk estimates. Second, individuals who died within 7 days after the onset of NOS were excluded to remove potentially susceptible cases. Third, individuals infected with COVID-19 before their first vaccination date or before their NOS diagnosis date were excluded, considering that COVID-19 infection itself might elevate seizure susceptibility [15]. Fourth, we employed a stricter definition of NOS by restricting the diagnosis to those identified through inpatient or emergency room visits only, thereby minimizing outcome misclassification. Lastly, we conducted a post-hoc analysis specifically among individuals vaccinated with mRNA-1273. All statistical analyses were performed using SAS Enterprise Guide version 8.3 (SAS Institute Inc., Cary, NC, USA).

Ethics statement

This study received approval from the Public Institutional Review Board Designated by Ministry of Health and Welfare (P01-202203-01-005) and adhered to the ethical principles outlined in the Declaration of Helsinki. Given the utilization of anonymized claims data in this study, the requirement for informed consent was waived. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline for cohort studies (Supplementary Material 3).

RESULTS

A total of 129,956,027 COVID-19 vaccine doses were administered in Korea during the study period. Among the 42,155,198 adults who received their first dose of a COVID-19 vaccine between February 26, 2021, and March 1, 2022, we identified 1,849 patients who experienced NOS within the designated risk window following vaccination. The mean age of the 1,849 patients who experienced NOS in the risk window was 54.6 years (standard deviation [SD], 19.7), while the mean age of the 4,217 patients who experienced NOS in the control window was 57.0 years (SD, 19.9). Women represented 768 (41.5%) of patients in the risk window and 1,800 (42.7%) of patients in the control window. Regarding comorbidities assessed during the year prior to the first vaccine dose, the Charlson comorbidity index was significantly higher in patients experiencing NOS in the control window (mean±SD, 1.9±2.3) compared with those in the risk window (mean±SD, 1.7±2.2). Patients in the control window also had a higher prevalence of dementia (n=715, 17.0% in the control window; n=255, 13.8% in the risk window) and chronic pulmonary disease (n=739, 17.5%; n=284, 15.4%). Diabetes mellitus (n=951, 22.6% in the control window; n=384, 20.8% in the risk window) and mild liver disease (n=934, 22.1%; n=394, 21.3%) were each prevalent in over 20% of patients experiencing NOS (Table 1).

As presented in Figure 2, the incidence of NOS was 1.52 per PY in the risk window and 1.54 per PY in the control window. The incidence of NOS increased gradually with each subsequent vaccine dose in both risk and control windows. Overall, there was no increased risk of NOS within 28 days following COVID-19 vaccination (IRR, 0.99; 95% CI, 0.94 to 1.05). Results from analyses stratified by first (IRR, 0.96; 95% CI, 0.89 to 1.05), second (IRR, 0.96; 95% CI, 0.88 to 1.04), third (IRR, 1.01; 95% CI, 0.90 to 1.13), and primary series doses (first and second doses combined; IRR, 0.97; 95% CI, 0.91 to 1.03) were consistent with the main analysis. Although subgroup analyses by vaccine type generally aligned with the main results (IRR, 0.95; 95% CI, 0.88 to 1.03 for BNT162b2; IRR, 0.95; 95% CI, 0.77 to 1.16 for ChAdOx1 nCoV-19; IRR, 1.58; 95% CI, 0.52 to 4.83 for Ad26.COV2.S), a marginally elevated risk was noted for recipients of mRNA-1273 (IRR, 1.21; 95% CI, 1.04 to 1.42). Post-hoc analyses among recipients of homologous mRNA-1273 vaccination indicated no increased risk for the first (IRR, 1.01; 95% CI, 0.79 to 1.29) or third doses (IRR, 1.29; 95% CI, 0.92 to 1.80), although a significantly elevated risk was observed after the second dose (IRR, 1.35; 95% CI, 1.09 to 1.67) (Supplementary Material 4).

Subgroup analyses stratified by age group, sex, insurance type, region, and comorbidities generally showed results consistent with the primary findings, indicating no increased NOS risk following vaccination. However, the age group of 30-39 years exhibited a slightly increased risk of NOS (IRR, 1.31; 95% CI, 1.10 to 1.55) (Table 2). All sensitivity analyses yielded findings consistent with the primary analysis (Figure 3).

DISCUSSION

This nationwide study found no increased risk of NOS within 28 days following COVID-19 vaccination. The main results were consistent across subgroup analyses categorized by age group, sex, vaccine dose, and underlying comorbidities. The robustness of these findings was further confirmed through multiple sensitivity analyses, including varying the risk window duration, restricting participants without COVID-19 infections, and applying a more stringent outcome definition.

To our knowledge, this study represents the largest population-based evaluation of the risk of NOS following COVID-19 vaccination conducted to date. Our findings align with those of a previous SCCS study from Hong Kong, which included 426 and 263 incident seizure cases following vaccination with BNT162b2 and CoronaVac, respectively [16]. That study reported no increased seizure risk during days 1 to 6 following BNT162b2 (IRR, 1.39; 95% CI, 0.75 to 2.58) or CoronaVac (IRR, 1.19; 95% CI, 0.50 to 2.83). Similarly, another SCCS study conducted in Malaysia found no significant association between vaccination with CoronaVac (IRR, 1.15; 95% CI, 0.91 to 1.44) or ChAdOx1-nCoV-19 (IRR, 1.47; 95% CI, 0.83 to 2.59) and seizure risk within a risk window of 1-21 days after vaccination [18]. Both previous studies assessed periods during which the B.1.617.2 (Delta) variant was dominant (before January 2022 in Korea [24]). Our findings support these prior studies with reassuring results covering the period when the B.1.1.529 (Omicron) variant was dominant (after January 2022), further reinforcing the safety profile across diverse types and doses of COVID-19 vaccines in a larger population, with more precise risk estimates.

The biological mechanisms underlying potential associations between COVID-19 vaccines and incident seizures remain unclear. Previous studies have suggested possible seizure risks associated with non-COVID-19 vaccines, including the measles, mumps, and rubella (MMR) vaccine, and the diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccine [14,25]. These traditional vaccines utilize platforms such as live attenuated or inactivated vaccines, whereas the COVID-19 vaccines studied here employ newer platforms, including lipid nanoparticle-encapsulated nucleoside-modified RNA vaccines (BNT162b2, mRNA-1273) [26,27], viral vector vaccines (ChAdOx1 nCoV-19, Ad26.COV2.S) [28,29], or protein-based vaccines (NVX-CoV2373) [30]. Potential mechanisms hypothesized as seizure triggers—such as immune-mediated abnormal neuronal activity or sudden hyperthermia causing increased blood-brain barrier permeability during fever response [31,32] — are not inherently specific to any particular vaccine platform. Indeed, our study found a slightly increased NOS risk with mRNA-1273, which was not observed for the analogous nucleic acid-based vaccine, BNT162b2. Comparative vaccine efficacy studies have reported more frequent reactogenicity-related adverse events, such as fever—potential seizure triggers—with mRNA-1273 compared to BNT162b2 [33]. This difference could be attributed to significantly greater humoral immunogenicity (higher antibody titers) observed among mRNA-1273 recipients [34,35]. It is plausible that variations in immune responses that can trigger seizures might contribute to differences in observed seizure risks. However, given inconsistent findings from analyses stratified by mRNA-1273 doses, the possibility of a chance finding cannot be excluded, highlighting the need for further research.

In our study, individuals with a prior seizure diagnosis were excluded to accurately identify incident seizure cases. While this approach enhanced the precision of our NOS assessment, it concurrently limited our ability to assess the risk of recurrent seizures following vaccination among people with epilepsy (PWE). The clinical concern regarding potential exacerbation of seizure symptoms following COVID-19 vaccination in PWE warrants further investigation. Multiple studies to date have consistently indicated that COVID-19 vaccines are well-tolerated by individuals with pre-existing epilepsy [36-39]. The favorable safety profiles observed in these studies offer encouraging evidence supporting vaccine confidence among the PWE population. Additional studies involving large cohorts of individuals with epilepsy are necessary to provide robust safety data in this important clinical context.

Our study has several strengths. First, using a comprehensive nationwide database allowed us to derive precise risk estimates despite the rarity of the outcome. Over 100 million vaccine doses were administered during the study period, including booster doses and multiple vaccine types, enabling a thorough safety assessment complementary to previous studies. Second, the SCCS analysis facilitated vaccine safety evaluations within a population characterized by high COVID-19 vaccination rates, using within-individual comparisons that effectively controlled for time-invariant confounders. Third, subgroup analyses stratified by various underlying comorbidities further reinforced the safety of COVID-19 vaccines for the majority of the population.

However, several limitations should be acknowledged. First, the SCCS analysis did not control for time-varying confounders. Given the observational nature of our study, we cannot exclude the possibility of residual confounding and thus cannot infer causality from our results. Second, the use of claims data—relying on diagnosis codes and drug prescriptions to define NOS—did not allow differentiation of seizure types based on symptomatic etiology or epileptiform electroencephalography patterns (e.g., generalized seizures, tonic-clonic seizures, absence seizures, myoclonic seizures, or febrile seizures), each of which has distinct etiologies and risk factors [40]. Furthermore, defining NOS cases as seizure diagnoses accompanied by same-day ASM prescriptions could have underestimated true incident seizure occurrences. Lastly, our study only included Korean individuals, potentially limiting the generalizability of the findings to other ethnic groups.

In conclusion, this nationwide study found no evidence of an increased risk of NOS following COVID-19 vaccination. Although a marginally increased risk was observed with the mRNA-1273 vaccine, further research is necessary to investigate the observed differences in risk across vaccine types. Given the small absolute risk of NOS identified in this study, our findings provide valuable real-world evidence from a large population, contributing to enhanced public confidence in COVID-19 vaccination programs.

Supplementary materials

NOTES

Conflict of interest

Ju Young Shin received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, and pharmaceutical companies, including LG Chem, UCB, SK bioscience, and Pfizer, outside the submitted work. The other authors have no conflicts of interest to declare for this study.

Ju Young Shin has been the deputy editor of the Epidemiology and Health since 2024. She was not involved in the review process.

Funding

This study was supported by a grant (grant No. 2021-05-008) of the Korea Disease Control and Prevention Agency.

Acknowledgements

The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript.

Author contributions

Conceptualization: Ko HY, Yoon D, Kim JH, Jeong HE, Shin JY. Data curation: Ko HY, Yoon D. Formal analysis: Ko HY, Yoon D. Funding acquisition: Shin JY. Methodology: Ko HY, Yoon D, Kim JH, Jeong HE, Hong SB, Shin WC, Shin JY. Project administration: Shin JY, Shin WC, Hong SB. Visualization: Ko HY. Writing – original draft: Ko HY, Yoon D, Kim JH, Jeong HE, Hong SB, Shin WC, Shin JY. Writing – review & editing: Ko HY, Yoon D, Shin JY.

Figure 1.

Flowchart of study participant selection. COVID-19, coronavirus disease 2019; ASMs, anti-seizure medications.

Figure 2.

Risk of new-onset seizures within 28 days following coronavirus disease 2019 vaccination, overall and stratified by vaccine doses, vaccination strategies, and vaccine platforms. IR, incidence rate; IRR, incidence rate ratio; CI, confidence interval; N/A, not available.

Figure 3.

Risk of new-onset seizures following coronavirus disease 2019 vaccination in the sensitivity analyses. IR, incidence rate; IRR, incidence rate ratio; CI, confidence interval; N/A, not available.

REFERENCES

• 1. Johns Hopkins University Coronavirus Resource Centre. COVID-19 dashboard [cited 2024 Jan 13]. Available from: https://coronavirus.jhu.edu/vaccines/international
• 2. World Health Organization. Ending the COVID-19 emergency and transitioning from emergency phase to longer-term disease management: guidance on calibrating the response, 4 September 2023 [cited 2024 Jan 13]. Available from: https://www.who.int/publications/i/item/WHO-WHE-SPP-2023.2
• 3. Notarte KI, Catahay JA, Velasco JV, Pastrana A, Ver AT, Pangilinan FC, et al. Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: a systematic review. EClinicalMedicine 2022;53:101624. https://doi.org/10.1016/j.eclinm.2022.101624ArticlePubMedPMC
• 4. Byambasuren O, Stehlik P, Clark J, Alcorn K, Glasziou P. Effect of covid-19 vaccination on long covid: systematic review. BMJ Med 2023;2:e000385. https://doi.org/10.1136/bmjmed-2022-000385ArticlePubMedPMC
• 5. Ghosh R, Dubey S, Roy D, Mandal A, Naga D, Benito-León J. Focal onset non-motor seizure following COVID-19 vaccination: a mere coincidence? Diabetes Metab Syndr 2021;15:1023-1024. https://doi.org/10.1016/j.dsx.2021.05.003ArticlePubMedPMC
• 6. Aladdin Y, Shirah B. New-onset refractory status epilepticus following the ChAdOx1 nCoV-19 vaccine. J Neuroimmunol 2021;357:577629. https://doi.org/10.1016/j.jneuroim.2021.577629ArticlePubMedPMC
• 7. Makhlouf AT, Van Alphen MU, Manzano GS, Freudenreich O. A seizure after COVID-19 vaccination in a patient on clozapine. J Clin Psychopharmacol 2021;41:689-690. https://doi.org/10.1097/JCP.0000000000001488ArticlePubMed
• 8. Werner J, Brandi G, Jelcic I, Galovic M. New-onset refractory status epilepticus due to autoimmune encephalitis after vaccination against SARS-CoV-2: first case report. Front Neurol 2022;13:946644. https://doi.org/10.3389/fneur.2022.946644ArticlePubMedPMC
• 9. Albsheer K, Fadul A, Abdalla E, Mohamed G, Elawad M, Zafar A. Post-COVID-19 vaccine limbic encephalitis: a case report. Cureus 2022;14:e29003. https://doi.org/10.7759/cureus.29003ArticlePubMedPMC
• 10. Mendu SB, Singavarapu PR, Kota V, Sheri AR, Kotha R Sr. Generalised tonic-clonic seizure in adolescents following COVID-19 vaccination: a case report on a mere co-incidence. Cureus 2023;15:e40992. https://doi.org/10.7759/cureus.40992ArticlePubMedPMC
• 11. Villagrán-Sancho D, Luque-Ambrosiani AC, Mayorga-Morón C, Gómez-Fernández FJ, Arzalluz-Luque J, Castela-Murillo A, et al. Cryptogenic new-onset super-refractory status epilepticus following SARS-CoV-2 vaccination. A case report. Rev Neurol 2023;76:399-402. (Spanish). https://doi.org/10.33588/rn.7612.2022374ArticlePubMedPMC
• 12. Bauman K, Rosenthal J, Lin J. New-onset refractory status epilepticus after Pfizer-BioNTech COVID-19 vaccination (P3-8.006). Neurology 2022;98(18 Suppl):3631. https://doi.org/10.1212/WNL.98.18_supplement.3631Article
• 13. Flammer J, Neziraj T, Rüegg S, Pröbstel AK. Immune mechanisms in epileptogenesis: update on diagnosis and treatment of autoimmune epilepsy syndromes. Drugs 2023;83:135-158. https://doi.org/10.1007/s40265-022-01826-9ArticlePubMedPMC
• 14. Sun Y, Christensen J, Hviid A, Li J, Vedsted P, Olsen J, et al. Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B. JAMA 2012;307:823-831. https://doi.org/10.1001/jama.2012.165ArticlePubMed
• 15. Vohora D, Jain S, Tripathi M, Potschka H. COVID-19 and seizures: Is there a link? Epilepsia 2020;61:1840-1853. https://doi.org/10.1111/epi.16656ArticlePubMedPMC
• 16. Wan EY, Ng VW, Chang RS, Yan VK, Chui CS, Wong CK, et al. Association between the risk of seizure and COVID-19 vaccinations: a self-controlled case-series study. Epilepsia 2022;63:3100-3110. https://doi.org/10.1111/epi.17436ArticlePubMedPMC
• 17. Wong CK, Lau KT, Xiong X, Au IC, Lai FT, Wan EY, et al. Adverse events of special interest and mortality following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines in Hong Kong: a retrospective study. PLoS Med 2022;19:e1004018. https://doi.org/10.1371/journal.pmed.1004018ArticlePubMedPMC
• 18. Ab Rahman N, Lim MT, Lee FY, Lee SC, Ramli A, Saharudin SN, et al. Risk of serious adverse events after the BNT162b2, CoronaVac, and ChAdOx1 vaccines in Malaysia: a self-controlled case series study. Vaccine 2022;40:4394-4402. https://doi.org/10.1016/j.vaccine.2022.05.075ArticlePubMedPMC
• 19. Jeong NY, Park H, Oh S, Jung SE, Kim DH, Shin HS, et al. A framework for nationwide COVID-19 vaccine safety research in the Republic of Korea: the COVID-19 Vaccine Safety Research Committee. Osong Public Health Res Perspect 2023;14:5-14. https://doi.org/10.24171/j.phrp.2023.0026ArticlePubMedPMC
• 20. Petersen I, Douglas I, Whitaker H. Self controlled case series methods: an alternative to standard epidemiological study designs. BMJ 2016;354:i4515. https://doi.org/10.1136/bmj.i4515ArticlePubMed
• 21. Zhu FC, Li YH, Guan XH, Hou LH, Wang WJ, Li JX, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet 2020;395:1845-1854. https://doi.org/10.1016/S0140-6736(20)31208-3ArticlePubMedPMC
• 22. García-Pérez J, González-Pérez M, Castillo de la Osa M, Borobia AM, Castaño L, Bertrán MJ, et al. Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: secondary analysis of the randomized CombiVacS study. EClinicalMedicine 2022;50:101529. https://doi.org/10.1016/j.eclinm.2022.101529ArticlePubMedPMC
• 23. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61:344-349. https://doi.org/10.1016/j.jclinepi.2007.11.008ArticlePubMed
• 24. Jeong SJ, An M, Jang M, Choi SY, Choi YJ, Jang J, et al. Severity of COVID-19 associated with SARS-CoV-2 variants dominant period in the Republic of Korea. Public Health Wkly Rep 2023;16:1464-1487. (Korean). https://doi.org/10.56786/PHWR.2023.16.43.2Article
• 25. Barlow WE, Davis RL, Glasser JW, Rhodes PH, Thompson RS, Mullooly JP, et al. The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine. N Engl J Med 2001;345:656-661. https://doi.org/10.1056/NEJMoa003077ArticlePubMed
• 26. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-2615. https://doi.org/10.1056/NEJMoa2034577ArticlePubMedPMC
• 27. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384:403-416. https://doi.org/10.1056/NEJMoa2035389ArticlePubMedPMC
• 28. Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020;396:467-478. https://doi.org/10.1016/S0140-6736(20)31604-4ArticlePubMedPMC
• 29. Sadoff J, Gray G, Vandebosch A, Cárdenas V, Shukarev G, Grinsztejn B, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med 2021;384:2187-2201. https://doi.org/10.1056/NEJMoa2101544ArticlePubMedPMC
• 30. Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med 2021;385:1172-1183. https://doi.org/10.1056/NEJMoa2107659ArticlePubMedPMC
• 31. Walter EJ, Carraretto M. The neurological and cognitive consequences of hyperthermia. Crit Care 2016;20:199. https://doi.org/10.1186/s13054-016-1376-4ArticlePubMedPMC
• 32. Kiyatkin EA, Sharma HS. Permeability of the blood-brain barrier depends on brain temperature. Neuroscience 2009;161:926-939. https://doi.org/10.1016/j.neuroscience.2009.04.004ArticlePubMedPMC
• 33. Chapin-Bardales J, Gee J, Myers T. Reactogenicity following receipt of mRNA-based COVID-19 vaccines. JAMA 2021;325:2201-2202. https://doi.org/10.1001/jama.2021.5374ArticlePubMed
• 34. Steensels D, Pierlet N, Penders J, Mesotten D, Heylen L. Comparison of SARS-CoV-2 antibody response following vaccination with BNT162b2 and mRNA-1273. JAMA 2021;326:1533-1535. https://doi.org/10.1001/jama.2021.15125ArticlePubMedPMC
• 35. Barbeau DJ, Martin JM, Carney E, Dougherty E, Doyle JD, Dermody TS, et al. Comparative analysis of human immune responses following SARS-CoV-2 vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. NPJ Vaccines 2022;7:77. https://doi.org/10.1038/s41541-022-00504-xArticlePubMedPMC
• 36. Fang X, Hu S, Han T, Yang T, Hu J, Song Y, et al. Effect of inactivated COVID-19 vaccines on seizure frequency in patients with epilepsy: a multicenter, prospective study. Front Immunol 2022;13:984789. https://doi.org/10.3389/fimmu.2022.984789ArticlePubMedPMC
• 37. Massoud F, Ahmad SF, Hassan AM, Alexander KJ, Al-Hashel J, Arabi M. Safety and tolerability of the novel 2019 coronavirus disease (COVID-19) vaccines among people with epilepsy (PwE): a cross-sectional study. Seizure 2021;92:2-9. https://doi.org/10.1016/j.seizure.2021.08.001ArticlePubMedPMC
• 38. Romozzi M, Rollo E, Quintieri P, Dono F, Evangelista G, Consoli S, et al. Impact of COVID-19 vaccine on epilepsy in adult subjects: an Italian multicentric experience. Neurol Sci 2022;43:4627-4634. https://doi.org/10.1007/s10072-022-06100-0ArticlePubMedPMC
• 39. Wang S, Lv J, He C, Yang Y, Zheng Y, Ye L, et al. COVID-19 vaccination hesitancy and safety among adult people with epilepsy in eastern China. Epilepsy Behav 2023;138:108984. https://doi.org/10.1016/j.yebeh.2022.108984ArticlePubMedPMC
• 40. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014;55:475-482. https://doi.org/10.1111/epi.12550ArticlePubMed

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