Abstract
Objective
This study assesses the hesitancy and safety of vaccination administration for the novel 2019 Coronavirus Disease (COVID-19) among adult people with epilepsy (PWE).
Methods
We recruited adult PWE who visited the outpatient epilepsy clinic from August 2021 to February 2022. We administered a structured questionnaire and a face-to-face interview regarding demographic factors, epilepsy characteristics, and relevant vaccine issues to all patients. Factors related to receiving a vaccine and epilepsy-related events after vaccination were then analyzed.
Results
A total of 501 PWE were surveyed; 288 were unvaccinated and 213 were vaccinated. Patients without jobs (OR: 0.59; 95% CI: 0.37–0.95, p = 0.03) were less likely to receive the vaccine compared to students or those with jobs. Other factors associated with vaccination were a higher number of anti-seizure medications (OR: 0.72; 95% CI: 0.55–0.95, p = 0.02) and a lower pre-vaccine seizure frequency (OR: 2.21; 95% CI: 1.06–4.59, p = 0.03). Of the 213 vaccinated patients, 10 (4.70%) reported at least one local and/or systemic side effect. Most patients (92.50%) did not report worse seizures within one month of vaccination. Poor ASM adherence (OR: 15.06; 95% CI: 1.75–129.87, p = 0.01) and fatigue/stimulant drinks such as caffeine (OR: 50.59; 95% CI: 7.57–337.94, p < 0.01) were significantly associated with seizure worsening within one month of receiving the COVID-19 vaccination.
Conclusion
Almost two-fifths of patients with adult PWE have received a COVID-19 vaccine. Attention should be paid to educating epilepsy patients without jobs on the significance and safety of the vaccine. There was a low risk of seizure worsening in the short term after vaccination in PWE.
Keywords: COVID-19 vaccine, Adult, People with epilepsy, Seizure worsening
1. Introduction
The coronavirus disease 2019 (COVID-19) led to a worldwide pandemic in December 2019 and has since tremendously impacted public health, especially for people with epilepsy (PWE) [1], [2]. It is well established that PWE has a higher cumulative COVID-19 incidence rate and a higher risk of mortality compared to the general population [2]. A mass immunization program is considered the best method of slowing the pandemic, and the COVID-19 vaccine is safe for the vast majority of people [3], [4], [5], [6], though there are some post-vaccination cases of demyelinating diseases, cerebral venous sinus thrombosis, and seizures among healthy people without epilepsy [7], [8], [9]. While there are a limited number of PWE in studies with COVID-19 vaccines [4], [5], [10], [11], [12] and a lack of emphasis on seizure worsening, the International League Against Epilepsy (ILAE) still recommended that PWE should get vaccinated. However, many PWE has been hesitant to get vaccinated [3], [10], [11], [12], [13], [14], [15].
To better outline this issue, this study aims to evaluate the safety of the vaccine and the causes of vaccination hesitancy among PWE.
2. Materials and methods
2.1. Study Design and participants
This is a cross-sectional observational study assessing COVID-19 vaccination in adult patients diagnosed with chronic epilepsy based on the ILAE classification [16], [17]. Included in the study are all individuals with epilepsy aged 18 years or older who visited our outpatient clinic between 27th August 2021 and 22nd February 2022. Questionnaires were administered through face-to-face interviews by trained investigators. All participants were asked to voluntarily complete the questionnaire by themselves or with the help of the interviewers if they had difficulty reading or writing. This study was approved by the institutional review board ethical guidelines of the Second Affiliated Hospital of Zhejiang University (SAHZU).
The questionnaire can be summarized in three parts: (1) COVID-19 vaccination status and, if vaccinated, information on the vaccine type, date of vaccination, general adverse effects (injection site pain, fever, fatigue, headache, diarrhea, etc.), and adverse effects (change in seizure frequency, new seizure types, and status epilepticus); (2) for unvaccinated patients, reasons for not being vaccinated including sociodemographic and epilepsy-specific factors; and (3) for unvaccinated patients, attitudes about future vaccination (willingness to be vaccinated, hesitation to be vaccinated, and refusal to be vaccinated).
The following sociodemographic data were obtained: age, gender, level of education, children, occupation, and marital status. Possible occupations were as follows: employed, student, and unemployed (including stay-at-home parents, retirees, or other). Epilepsy characteristics were also collected, including seizure onset, epilepsy duration, seizure type, drug-resistant epilepsy, seizure frequency, history of bilateral tonic-clonic seizures (BTCS), anti-seizure medications (ASMs), and magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) findings. Epilepsy was diagnosed according to the ILAE 2017 definition [16], [17], which was classified as focal, generalized, or unknown. Drug-resistant epilepsy was defined as patients who were not seizure-free in the previous 12 months despite having received adequate-dose treatments of two or more ASMs [18]. Seizure frequency before vaccination was categorized as a grading variable, with options of at least 1-year seizure-free, at least once per year, once every month, and once every week [3]. Seizure changes were recorded from the first day to one month of vaccination. Postvaccine fever was defined as a temperature >37.3 °C within 7 days after vaccination.
2.2. Statistical analysis
The acquired data were presented as the median (interquartile range) using SPSS statistical analysis software (version 23). A nonparametric Mann-Whitney U test was used to compare group differences on continuous variables. Categorical variables were analyzed by Pearson’s chi-square test or Fisher’s exact test. Univariate analysis results were entered into a multivariable binary logistic regression model with a statistical significance of p ≤ 0.05. A stepwise logistic regression analysis was applied to determine unique related factors between several variables related to worsening seizures after vaccination, with a statistical significance of p < 0.05. The odds ratio (OR) and 95% confidence interval (CI) were also calculated for each parameter.
3. Results
3.1. Cohort characteristics
A total of five hundred and one patients were enrolled in this study (213 vaccinated and 288 non-vaccinated). Fig. 1 shows the detailed age distribution in the study. Over half of those who participated in this study were aged 30 years or younger both in the enrolled cohort and the vaccinated subgroup. There was no significant difference in age distribution between the whole group and the vaccinated subgroup. None previously. Fatigue and pain at the injection site were the most common side effects, followed by diarrhea, headache, and chest tightness. Fever was only reported by one person on the day after the first injection.
Fig. 1.
Age distribution in the entire cohort and vaccinated group. Abbreviations Y = Year.
The clinical features of vaccinated and unvaccinated patients are shown in Table 1 . Level of education (≧high school), job status, pharmacoresistant epilepsy, seizure frequency, history of BTCS within one year, number of seizure types, number of ASMs, and MRI findings were set as independent variables in the logistic regression. The results found that the median number of ASMs (OR 0.72, 95% CI 0.55–0.95, p = 0.02) and unemployed patients (OR 0.59, 95% CI 0.37–0.95, p = 0.03) were negatively associated with being vaccinated while a seizure frequency of less than once a year (OR 2.21, 95% CI 1.06–4.59, p = 0.03) was significantly associated with being vaccinated (Table 2 ). 56.30% of the vaccinated patients experienced at least six seizure-free months after ASM therapy, which was higher than (29.50%) in the unvaccinated group (p < 0.01, Figure 2 ) and similar to the results after 12 months (46.90% vs. 23.60%, p < 0.01).
Table 1.
Comparison of clinical characteristics between patients with and without COVID-19 vaccines.
| Demographic variables | Whole (N = 501) | Vaccinated (N = 213) | Not vaccinated (N = 288) | P-value |
|---|---|---|---|---|
| Age, Y (IQR) | 29.00 (23.00–39.50) | 28.00 (23.00–38.00) | 29.50 (24.00–41.00) | 0.37c |
| Gender, male | 251 (50.10%) | 107 (50.23%) | 144 (50.00%) | 0.96a |
| Level of education,≧high school | 340 (67.86%) | 157 (73.71%) | 183 (63.5%) | 0.02a |
| Marital status | 0.27b | |||
| Unmarried | 257 (51.30%) | 114 (53.52%) | 143 (49.65%) | |
| Married | 237 (47.31%) | 98 (46.01%) | 139 (48.26%) | |
| Divorced/widow | 7 (1.40%) | 1 (0.47%) | 6 (2.08%) | |
| Procreated | 217 (43.31%) | 88 (41.31%) | 129 (44.79%) | 0.44a |
| Occupation | ||||
| Unemployed | 127 (25.35%) | 39 (18.31%) | 88 (30.56%) | <0.01a |
| Employed | 292 (58.3%) | 133 (62.44%) | 159 (55.21%) | 0.11a |
| Student | 82 (16.37%) | 41 (19.25%) | 41 (14.24%) | 0.13a |
| Seizure onset, Y, median (IQR) | 18.00 (14.00–27.00) | 18.00 (13.00–27.00) | 19.00 (14.00–28.00) | 0.53c |
| Epilepsy duration, M, median (IQR) | 96.00 (48.00–180.00) | 96.00 (48.00–168.00) | 96.00 (48.00–204.00) | 0.30c |
| Seizure type | 0.10a | |||
| Focal onset | 453 (90.42%) | 186 (87.32%) | 267 (92.71%) | |
| Generalized onset | 39 (7.78%) | 23 (10.80%) | 16 (5.56%) | |
| Unknown onset | 9 (1.80%) | 4 (1.88%) | 5 (1.74%) | |
| Pharmacoresistant epilepsy | 167 (33.33%) | 35 (16.43%) | 132 (45.83%) | <0.01a |
| Seizure frequency | <0.01a | |||
| At least once per week | 75 (14.97%) | 20 (9.39%) | 55 (19.10%) | |
| At least one per month | 120 (23.95%) | 35 (16.43%) | 85 (29.51%) | |
| At least one per year | 140 (27.94%) | 57 (26.76%) | 83 (28.82%) | |
| Less than once every year | 166 (33.13%) | 101 (47.42%) | 65 (22.57%) | |
| History of BTCS | 327 (65.27%) | 137 (64.32%) | 190 (65.97%) | 0.70a |
| History of BTCS within one year | 161 (32.14%) | 50 (23.47%) | 111 (38.54%) | <0.01a |
| Number of seizure types, median (IQR) | 1.00 (1.00–2.00) | 1.00 (1.00–2.00) | 1.00 (1.00–2.00) | <0.01c |
| Number of ASMs, median (IQR) | 1.00 (1.00–2.00) | 1.00 (1.00–2.00) | 2.00 (1.00–2.00) | <0.01c |
| MRI finding | 0.04a | |||
| Normal | 233 (50.1%) | 109 (51.17%) | 124 (43.06%) | |
| Abnormal | 232 (49.9%) | 87 (40.85%) | 145 (50.35%) | |
| EEG finding, presence of IEDs | 225 (49.8%) | 90 (42.25%) | 135 (46.88%) | 0.25a |
Abbreviation: COVID = Coronavirus disease; IQR = interquartile range; M = month; BTCS = bilateral tonic-clonic seizure; ASMs = anti-seizure medications; MRI = Magnetic Resonance Imaging; EEG = Electroencephalography; IEDs = interictal epileptiform discharges.
Pearson’s chi-square test.
Fisher‘s exact test.
Nonparametric Mann-Whitney U test.
Table 2.
Logistic analysis of predictors for taking the COVID-19 vaccine among adult people with epilepsy.
| Variables | 95% CI | OR | P value |
|---|---|---|---|
| Level of education, ≧high school | 0.83–2.03 | 1.30 | 0.25 |
| Occupation | |||
| Unemployed | 0.37–0.95 | 0.59 | 0.03 |
| Pharmacoresistant epilepsy | 0.30–1.03 | 0.55 | 0.06 |
| Seizure frequency | |||
| Several times per week | 1 | ||
| Several times per month | 0.64–2.62 | 1.30 | 0.47 |
| Several times per year | 0.55–2.26 | 1.11 | 0.77 |
| Less than once every year | 1.06–4.59 | 2.21 | 0.03 |
| History of BTCS within one year | 0.44–1.21 | 0.73 | 0.22 |
| Number of seizure types | 0.50–1.04 | 0.72 | 0.08 |
| Number of ASMs | 0.55–0.95 | 0.72 | 0.02 |
| MRI finding, abnormal | 0.62–1.42 | 0.94 | 0.77 |
Abbreviations: COVID = Coronavirus disease; CI = confidence interval; OR = odds ratio;
BTCS = bilateral tonic clonic seizure; ASMs = anti-seizure medications; MRI = Magnetic Resonance Imaging.
Fig. 2.
Proportion of seizure-free rate among four groups. The asterisk represents the difference between the seizure-free rate between unvaccinated and vaccinated groups within 6 (p < 0.001) and 12 (p < 0.001) months. Abbreviation: ASMs = anti-seizure medications; SF = seizure-free; n-SF = non-seizure-free; m = months.
Of the 288 unvaccinated patients, 108 (37.50%) were willing to receive the COVID-19 vaccine within the following six months. The main reasons for refusing or hesitance about the COVID-19 vaccine were fear of vaccine safety and fear of seizure worsening, followed by other co-existing diseases, pregnancy, history of severe allergies, breastfeeding, and planning to become pregnant (Table 3 ). A significant association was found between unwillingness to receive the COVID-19 vaccine and fear of worsening seizures (p = 0.01).
Table 3.
Factors associated with COVID-19 vaccine hesitancy or refusal in the future six months.
| Variables | Hesitated or unwilling to receive vaccines (N = 180) | Willing to receive vaccines (N = 108) | P value |
|---|---|---|---|
| Co-exist other diseases | 13 (7.22%) | 8 (7.41%) | 0.95a |
| Breast-feeding | 0 | 1 (0.93%) | 0.38b |
| Pregnancy | 2 (1.11%) | 2 (1.85%) | 0.63b |
| Ready to be pregnant | 1 (0.56%) | 0 | 1.00b |
| Fear of vaccine safety | 105 (58.33%) | 73 (67.59%) | 0.10a |
| Fear of seizure worsening | 160 (88.89%) | 84 (77.78%) | 0.01a |
| History of severe allergies | 3 (1.67%) | 1 (0.93%) | 1.00b |
Abbreviation: COVID = Coronavirus disease.
Pearson’s chi-square test.
Fisher’s exact test.
In the vaccinated group, sixteen patients (7.50%) experienced typical seizure worsening within 1 month post-vaccination, including eight patients after receiving the first dose, seven after the second dose, and one after the third dose. No episode of status epilepticus was reported. Among them, we found that there were eleven patients whose therapy changed after vaccination (seven with starting ASM therapy; three with increased their ASMs dose; one with the addition of a new ASM). Univariate analysis found late seizure onset (p = 0.05), few ASMs (p = 0.05), poor ASM adherence (p = 0.03), and fatigue or stimulant drinks such as coffee (p < 0.001) were common in patients suffering from seizure worsening after vaccination (Table 4 ). Logistic regression analysis found that poor ASM adherence (OR 15.06, 95% CI 1.75–129.87, p = 0.01) and fatigue/stimulant drinks such as coffee (OR 50.59, 95% CI 7.57–337.94, p < 0.01) were significantly associated seizure worsening in PWE after vaccination (Table 5 ).
Table 4.
Clinical characteristics and seizure worsening within one month after vaccination in people with epilepsy.
| Variables | Whole cohort (N = 213) | Non-seizure aggravation (N = 197) | Seizure aggravation (N = 16) | P-value |
|---|---|---|---|---|
| Age (IQR) | 28.00 (23.00–38.00) | 27.00 (23.00–38.00) | 32.00 (25.00–40.00) | 0.27c |
| Gender, male | 107 (50.23%) | 100 (50.76%) | 7 (43.75%) | 0.59a |
| Seizure onset, Y, median (IQR) | 18.00 (13.00–27.00) | 18.00 (13.00–26.50) | 24.50 (15.75–37.75) | 0.05c |
| Epilepsy duration, M, median (IQR) | 96.00 (48.00–168.00) | 96.00 (48.00–168.00) | 69.00 (15.00–126.00) | 0.08c |
| Pharmacoresistant epilepsy | 35 (16.43%) | 33 (16.75%) | 2 (12.50%) | 1.00b |
| Seizure type | 0.77b | |||
| Focal onset | 186 (87.32%) | 172 (87.31%) | 14 (87.50%) | |
| Generalized onset | 23 (10.80%) | 21 (10.66%) | 2 (12.50%) | |
| Unknown onset | 4 (1.88%) | 4 (2.03%) | 0 | |
| Number of seizure types, median (IQR) | 1.00 (1.00–2.00) | 1.00 (1.00–2.00) | 1.0 (1.00–2.00) | 0.41c |
| Seizure frequency | 0.85b | |||
| Several times per week | 20 (9.39%) | 19 (9.64%) | 1 (6.25%) | |
| Several times per month | 35 (16.43%) | 33 (16.75%) | 2 (12.50%) | |
| Several times per year | 57 (26.76%) | 51 (25.89%) | 6 (37.50%) | |
| Less than once every year | 101 (47.42%) | 94 (47.72%) | 7 (43.75%) | |
| History of BTCS | 137 (64.32%) | 127 (64.47%) | 10 (62.50%) | 0.87a |
| History of BTCS within one year | 50 (23.47%) | 48 (24.37%) | 2 (12.50%) | 0.44a |
| Number of ASMs, median (IQR) | 1.00 (1.00–2.00) | 1.00 (1.00–2.00) | 1.00 (0–1.75) | 0.05c |
| MRI finding, abnormal | 87 (40.85%) | 81 (41.12%) | 6 (37.50%) | 0.72a |
| EEG finding, presence of IEDs | 90 (42.25%) | 83 (42.13%) | 7 (43.75%) | 1.00a |
| Poor ASM adherence | 4 (1.88%) | 2 (1.02%) | 2 (12.50%) | 0.03b |
| Fatigue or stimulant drinks | 6 (2.82%) | 2 (1.02%) | 4 (25.00%) | <0.01b |
| Seizure free within six months | 121 (56.81%) | 113 (57.36%) | 8 (50.00%) | 0.57a |
Abbreviation: IQR = interquartile range; BTCS = bilateral tonic-clonic seizure; ASMs = anti-seizure medications; MRI = Magnetic Resonance Imaging; EEG = Electroencephalography.
Pearson’s chi-square test.
Fisher‘s exact test.
Nonparametric Mann-Whitney U test.
Table 5.
Logistic regression analysis of variables associated with seizure aggravation after vaccination.
| Variables | 95% CI | OR | P-value |
|---|---|---|---|
| Age onset | 1.00–1.07 | 1.03 | 0.05 |
| Number of ASMs, median (IQR) | 0.31–1.27 | 0.62 | 0.20 |
| Poor ASM adherence | 1.75–129.87 | 15.06 | 0.01 |
| Fatigue or stimulant drinks | 7.57–337.94 | 50.59 | <0.01 |
Abbreviations: CI = confidence interval; OR = odds ratio; ASMs = anti-seizure medications.
4. Discussion
Our study reported on vaccination coverage, vaccination willingness, variables associated with being vaccinated, and seizure aggravation after vaccination during a short-term follow-up among adult people with epilepsy in eastern China.
We found that 42.51% of patients had been vaccinated against COVID-19, which was slightly higher than previous studies assessing adult PWE in China in recent months [3], [11], [19], and dramatically lower than the general population [3]. Increased awareness about the importance and safety of the vaccine in China is responsible for increases in the vaccination rate. The herd immunity threshold to extinguish SARA-CoV-2 is estimated to be between 55% and 82% [20], and the vaccination rate among PWE is still far below this threshold. PWE are more hesitant than others to accept the COVID-19 vaccine mainly due to a fear of worsening seizures [13]. The occurrence of adverse events in the present study was lower than in some previous studies [5], [6], [12], [21]. First, different vaccine types could help explain this phenomenon. It has been reported that having a local adverse event after vaccination is significantly more frequent with mRNA vaccines than with inactivated vaccines [6]. In this study, all people received inactivated vaccines, except for one person who received recombinant novel Coronavirus vaccines. The majority of people in reported studies with PWE received mRNA vaccines [5], [6], [12], [21]. Clinical trials of vaccines have demonstrated that local adverse events occurred more frequently in patients with mRNA vaccines (83% after the first dose; 78% after the second dose) than in those with inactivated vaccines (overall 2.7%) [22], [23], and the rate was even lower than that of this study. Moreover, advances in vaccine technology are important for the low rate of adverse events while vaccinating a large number of people during the pandemic. Another reason could be racial differences between study populations.
We analyzed potential factors associated with receiving the vaccine and found that patients without jobs, patients with many ASMs, and patients with a high seizure frequency were less likely to receive the COVID-19 vaccination. It is unsurprising that unemployed patients were less likely to be vaccinated. First, there is speculation that jobless patients are less socially connected and have less access to information about current affairs than others. Therefore, they could have insufficient awareness about vaccine importance and safety. One study suggested that COVID-19 risk perception was found to be significantly associated with vaccine acceptance [24]. Second, people without jobs might have more frequent seizures and a huge social stigma or concerns about occupational safety. This scenario could further result in increased unemployment and people without jobs also have great concerns regarding the safety of the vaccine. Third, if the classmates or colleagues of PWE are vaccinated, it could affect their willingness to obtain a vaccination. This emphasizes the importance of spreading vaccine awareness, particularly for those not associated with a school or place of work. The scientific community should also continue to stress the safety and efficacy of the COVID-19 vaccine. Vaccine hesitancy is a global issue, especially for PWE. Consistent with previous studies [10], [11], patients affected by poor-controlled epilepsy were unwilling to get vaccinated primarily because they were concerned about their epilepsy worsening, which is the key epilepsy-related factor in delayed vaccination. Another factor for vaccine hesitancy was concerns regarding nonepileptic adverse effects [3], [5]. False beliefs about infections stemming from a vaccine were also associated with vaccine hesitancy [13], which would gradually decrease due to public education campaigns.
The most common adverse reaction or concerns about the inactivated vaccine were febrile reactions and autoimmune disorders [25]. Only one person reported having a fever within a week after receiving the second dose and did not experience a seizure. Some studies have reported on the attitudes, coverage, and general side effects of COVID-19 vaccines in people with epilepsy [3], [10], [11], [13], [14], but few have focused on epilepsy-related adverse effects [4], [12], [15]. In some cases, obtaining a vaccinated cohort was difficult [4], [12], making the conclusions less robust. In the vaccinated group, sixteen patients (7.50%) experienced seizure worsening, and all seizures in this study were habitual. No patients experienced status epilepticus. One multicenter study from Italy suggested that 7.65% (25/327) of people with epilepsy suffered from worsening seizures after vaccination, which was based on the mean monthly change in seizures [15]. A multicenter report out of China demonstrated that 9.31% (19/204) of patients experienced seizure worsening, with the seizure frequency change assessed from the first injection until 1 week later [3]. One study of 82 vaccinated patients from Kuwait found that most patients (93.90%) did not report seizures worsening at least one week after vaccination [5]. Another study of 54 people with epilepsy from Germany reported that one person experienced increased seizure frequency one day after receiving the first COVID-19 vaccine and another one with the occurrence of a new seizure type [12]. In general, the COVID-19 vaccine has a low risk of epilepsy worsening and is well-tolerated among PWE in the short term. However, future investigations into long-term vaccine effects in a large cohort are still needed.
Our multivariate analysis demonstrated that patients with poor ASM adherence or fatigue/stimulant drinks were more likely to suffer from seizure exacerbation within one month of being vaccinated. In the current study, patients felt fatigued mainly due to high-intensity work and insomnia after vaccination, and “stimulant drinks” were considered drinks such as common coffee. Epilepsy worsening might not be a direct effect of the vaccine, even if the seizure frequency was more severe than before. As previous studies suggested, ASM adherence [26] and caffeine intake [27] are associated with seizure control in PWE. Vaccines could affect patients whose condition worsened due to unstable cortical excitability because of poor ASM adherence or fatigue/stimulant drinks. However, it remains unclear whether vaccines play a role in seizure worsening. Additionally, there was no control group of unvaccinated patients that was observed around the same time. It is unclear whether normal variability in seizure control can explain these results. Therefore, our findings must be confirmed in a case-control prospective study. One recent study reported that only pre-vaccine seizure frequency was associated with seizure worsening in vaccinated patients, which suggests that uncontrolled epilepsy could affect post-vaccine seizure frequency rather than be a direct effect of the vaccine [15]. Other studies failed to identify the potential risks of seizure worsening after vaccination due to small sample sizes [4], [5], [12].
This was a short-term study that estimated the safety and efficacy of the COVID-19 vaccines; however, more extensive, and long-term studies are required in the future. Importantly, no control group was included, making it unclear how much normal variability in seizure control accounts for the seizure worsening. Future research with additional subgroups such as persons with mental comorbidities or children is needed to fully demonstrate vaccine safety in PWE.
5. Conclusion
This study demonstrates that almost two-fifths of people with epilepsy have received the COVID-19 vaccine. Education focusing on increasing the vaccination rate in PWE is needed, especially for individuals who do not work. The risk of seizure worsening after vaccination was minimal in the short term. Poor ASM adherence or fatigue due to insufficient rest periods or regularly taking stimulant drinks could be associated with seizure worsening after vaccination; however, these findings must be confirmed in a case-control prospective study.
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.
Acknowledgments
This work was supported by the National Natural Science Foundation of China [Grant Numbers: 82001365, 82071443].
References
- 1.Siahaan Y.M.T., Ketaren R.J., Hartoyo V., Hariyanto T.I. Epilepsy and the risk of severe coronavirus disease 2019 outcomes: A systematic review, meta-analysis, and meta-regression. Epilepsy Behav. 2021;125:108437. doi: 10.1016/j.yebeh.2021.108437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Cabezudo-Garcia P., Ciano-Petersen N.L., Mena-Vazquez N., Pons-Pons G., Castro-Sanchez M.V., Serrano-Castro P.J. Incidence and case fatality rate of COVID-19 in patients with active epilepsy. Neurology. 2020;95:e1417–e1425. doi: 10.1212/WNL.0000000000010033. [DOI] [PubMed] [Google Scholar]
- 3.Lu L., Zhang Q., Xiao J., Zhang Y., Peng W., Han X., et al. COVID-19 vaccine take-up rate and safety in adults with epilepsy: Data from a multicenter study in China. Epilepsia. 2022;63:244–251. doi: 10.1111/epi.17138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Lu Q., Wang Y.Y., Wang Q.H., Tang L.N., Yang X.Y., Dun S., et al. Safety of inactivated COVID-19 vaccine in tuberous sclerosis complex patients with epilepsy treated with rapamycin. Seizure. 2022;99:71–74. doi: 10.1016/j.seizure.2022.05.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Massoud F., Ahmad S.F., Hassan A.M., Alexander K.J., 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. doi: 10.1016/j.seizure.2021.08.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ozdemir H.N., Dere B., Gokcay F., Gokcay A. Are COVID-19 vaccines safe for people with epilepsy? A cross-sectional study. Neurol Sci. 2022;43:3489–3496. doi: 10.1007/s10072-022-05956-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Khayat-Khoei M., Bhattacharyya S., Katz J., Harrison D., Tauhid S., Bruso P., et al. COVID-19 mRNA vaccination leading to CNS inflammation: a case series. J Neurol. 2022;269:1093–1106. doi: 10.1007/s00415-021-10780-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Wen S., Huang K., Zhu H., Li P., Zhou L., Feng L. Case Report: Anti-NF186+ CIDP After Receiving the Inactivated Vaccine for Coronavirus Disease (COVID-19) Front Neurol. 2022;13 doi: 10.3389/fneur.2022.838222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Frontera J.A., Tamborska A.A., Doheim M.F., Garcia-Azorin D., Gezegen H., Guekht A., et al. Neurological Events Reported after COVID-19 Vaccines: An Analysis of VAERS. Ann Neurol. 2022 doi: 10.1002/ana.26339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Li N., Chu C., Lin W. A Survey of Hesitancy and Response to the COVID-19 Vaccine Among Patients With Epilepsy in Northeast China. Front Neurol. 2021;12 doi: 10.3389/fneur.2021.778618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Qiao S., Zhang R.R., Yang T.T., Wang Z.H., Fang X.Q., Fang C.Y., et al. Attitudes to Being Vaccinated Against COVID-19: A Survey of People With Epilepsy in China. Front Neurol. 2021;12 doi: 10.3389/fneur.2021.743110. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.von Wrede R., Pukropski J., Moskau-Hartmann S., Surges R., Baumgartner T. COVID-19 vaccination in patients with epilepsy: First experiences in a German tertiary epilepsy center. Epilepsy Behav. 2021;122 doi: 10.1016/j.yebeh.2021.108160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Puteikis K., Mameniskiene R. Factors Associated with COVID-19 Vaccine Hesitancy among People with Epilepsy in Lithuania. Int J Environ Res Public Health. 2021;18 doi: 10.3390/ijerph18084374. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Asadi-Pooya A.A., Barzegar Z., Sadeghian S., Nezafat A., Shahisavandi M., Nabavizadeh S.A. COVID-19 Vaccine Hesitancy Among Patients With Epilepsy or Other Chronic Conditions. Disaster Medicine and Public Health Preparedness. 2021 doi: 10.1017/dmp.2021.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.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 doi: 10.1007/s10072-022-06100-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Scheffer I.E., Berkovic S., Capovilla G., Connolly M.B., French J., Guilhoto L., et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512–521. doi: 10.1111/epi.13709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Fisher R.S., Acevedo C., Arzimanoglou A., Bogacz A., Cross J.H., Elger C.E., et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475–482. doi: 10.1111/epi.12550. [DOI] [PubMed] [Google Scholar]
- 18.Kwan P., Schachter S.C., Brodie M.J. Drug-resistant epilepsy. N Engl J Med. 2011;365:919–926. doi: 10.1056/NEJMra1004418. [DOI] [PubMed] [Google Scholar]
- 19.Li N., Chu C.J., Lin W.H. A Survey of Hesitancy and Response to the COVID-19 Vaccine Among Patients With Epilepsy in Northeast China. Front Neurol. 2021;12 doi: 10.3389/fneur.2021.778618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Sanche S., Lin Y.T., Xu C., Romero-Severson E., Hengartner N., Ke R. High Contagiousness and Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2. Emerg Infect Dis. 2020;26:1470–1477. doi: 10.3201/eid2607.200282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.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. doi: 10.1007/s10072-022-06100-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Polack F.P., Thomas S.J., 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. doi: 10.1056/NEJMoa2034577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Tanriover M.D., Doganay H.L., Akova M., Guner H.R., Azap A., Akhan S., et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021;398:213–222. doi: 10.1016/S0140-6736(21)01429-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Nusair M.B., Arabyat R., Khasawneh R., Al-Azzam S., Nusir A.T., Alhayek M.Y. Assessment of the relationship between COVID-19 risk perception and vaccine acceptance: a cross-sectional study in Jordan. Hum Vaccin Immunother. 2022;18:2017734. doi: 10.1080/21645515.2021.2017734. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Lu L., Xiong W., Mu J., Zhang Q., Zhang H., Zou L., et al. The potential neurological effect of the COVID-19 vaccines: A review. Acta Neurol Scand. 2021;144:3–12. doi: 10.1111/ane.13417. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Zena D., Tadesse A., Bekele N., Yaregal S., Sualih N., Worku E. Seizure control and its associated factors among epileptic patients at Neurology Clinic, University of Gondar hospital, Northwest Ethiopia. SAGE Open Med. 2022;10 doi: 10.1177/20503121221100612. 20503121221100612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Bourgeois-Vionnet J., Ryvlin P., Elsensohn M.H., Michel V., Valton L., Derambure P., et al. Coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy. Epilepsy Behav. 2022;126 doi: 10.1016/j.yebeh.2021.108486. [DOI] [PubMed] [Google Scholar]