Experiences from COVID‐19 vaccination in patients with epilepsy

Abstract

Objective

This study aimed to investigate the safety of coronavirus disease 2019 (COVID‐19) vaccination in patients with epilepsy (PWE) and their willingness to undergo vaccination.

Methods

This study was a survey the survey questionnaire, which included general, epilepsy‐specific, and COVID‐specific questions, was completed by patients of the outpatient clinic and hospital ward at The Third Xiangya Hospital in 2021.

Results

A total of 120 valid questionnaires were returned. Eighty‐nine of 120 responders (74.2%) were not vaccinated, and 31 (25.8%) were vaccinated against COVID‐19. Of the 31 vaccinated PWE, one (3.2%) had worsening of seizures and four (12.9%) had adverse reactions that were characteristic of the COVID‐19 vaccine. The other 26 patients (83.9%) reported no adverse reactions, Moreover, there was no significant difference between the 18 PWE with well‐controlled seizures and the 13 PWE with poorly‐controlled seizures. Of the 89 unvaccinated PWE, 69.7% (62/89) were willing to receive the COVID‐19 vaccine, 28.1% (25/89) were unsure, and 2.2% (2/89) declined to be vaccinated.

Significance

Among PWE, few adverse reactions occurred following the COVID‐19 vaccination. Most PWE were willing to receive the COVID‐19 vaccine. COVID‐19 vaccination is safe for PWE.

Abbreviations

BBB

blood–brain barrier

CNS

central nervous system

COVID‐19

coronavirus disease 2019

NCoV

novel coronavirus

PWE

patients with epilepsy

SUDEP

sudden unexpected death in epilepsy

Key points.

1. In this paper, we investigated 120 PWEs, to survey their attitude on COVID‐19 vaccine and vaccination status.

2. To investigate the safety of COVID‐19 vaccination in PWEs and provide evidence to advise on vaccinating PWEs against COVID‐19.

1. INTRODUCTION

At the end of 2019, ¹ a new type of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2),was discovered, and was later named the novel coronavirus (NCoV). Eventually, the disease it caused was named novel coronavirus pneumonia and later the coronavirus disease 2019 (COVID‐19). ²

The primary modes of transmission of COVID‐19 are respiratory droplets and direct contact. ¹ COVID‐19 has spread rapidly worldwide, especially in densely populated areas. As people are in closer proximity and interact more frequently, transmission risk increase. Consequently, the transmission of COVID‐19 is difficult to effectively control. The rapid spread of the virus has led to a global pandemic. To date, there are many newly confirmed cases and deaths related to COVID‐19 daily. According to the World Health Organization, as of September 21, 2021, 2 389 510 549 people have been fully vaccinated and 228 807 631 confirmed cases of COVID‐19 have been reported worldwide, including 4 697 099 deaths. Currently, there is no high‐quality evidence from randomised double‐blind placebo‐controlled studies demonstrating that existing or new antiviral drugs can effectively treat COVID‐19. Because there is no effective treatment or curative method for COVID‐19, it is crucial to adopt an active preventive strategy. Population‐based immunisation against COVID‐19 may be the key to control or alleviate the COVID‐19 pandemic. ³

Epilepsy is a common neurological disease worldwide. ⁴ The prevalence of epilepsy is approximately 5‐8 per 1000 persons in industrialised contries. ⁵ The onset of epileptic episodes is usually unpredictable, and seizures often lead to accidents, including sudden unexpected death in epilepsy (SUDEP). Studies have confirmed that objective and subjective stress can aggravate seizures in patients with epilepsy (PWE). Infection, inflammation, neurodegenerative disorders, brain tumors, and brain injuries are common causes of epilepsy. For more than 120 years, studies have shown that the immune system plays an important role in the pathogenesis of epilepsy. ⁶ Recent studies have suggested that abnormal activation of inflammatory processes contributes to epilepsy. Inflammation may begin in the central nervous system (CNS), or systemic inflammation may breach the damaged blood–brain barrier (BBB) to reach the CNS. ⁷ Therefore, changes in the systemic immune system or variations in local neuro‐immunological responses may aggravate epileptic seizures.

Vaccination is a classic immunotherapy. COVID‐19 can be targeted via vaccination. All COVID‐19 vaccines are immunogenic. They simultaneously activate the humoral and cellular immune responses and stimulate the body's immune system to produce neutralizing antibodies against SARS‐CoV‐2. ⁸ As COVID‐19 works by modifying the host immune response, there are concerns regarding the safety of COVID‐19 vaccinations in PWE. According to a statement issued by the United Kingdom Joint Committee on Vaccines and Immunization, ⁹ certain underlying health conditions, such as chronic neurological diseases including epilepsy, increase the risk of morbidity and death from COVID‐19. Therefore, this study aimed to investigate the safety of COVID‐19 vaccination in PWE and their willingness to be vaccinated.

2. METHODS

2.1. Participants

We selected PWE from the outpatient and inpatient departments of The Third Xiangya Hospital. The inclusion criteria included were adults, aged between 18 and 60 years, with good communication and comprehension skills, the ability to complete the questionnaire independently, and no other contraindications for vaccination.

2.2. Method

The survey tool was a self‐report questionnaire based on relevant domestic and foreign literature. The content included (1) general demographic information, (2) basic information on epilepsy, (3) COVID‐19 vaccine awareness, and (4) vaccination status of PWE.

The questionnaire was disseminated using a QR code, and administered. from July to September 2021. To complete the questionnaire, the patient was asked to scan the hospital inpatient or outpatient clinic codes and their doctor–patient follow‐up group. Before the investigation, patients were fully informed of the questionnaire items. The patients provided informed consent and voluntarily completed the self‐reported questionnaire.

2.3. Statistical method

All questionnaire data were exported to Excel 2010. SPSS (version 21.0 IBM Corp) was used to analyse the data and express the frequency and percentage of COVID‐19 vaccination and cognition in PWE.

3. RESULTS

The participants' characteristics are shown in Table 1. A total of 120 PWE completed the questionnaire. Of these, 66 (55%) were men and 54 (45%) were women. The willingness of the patients to receive a COVID‐19 vaccination is shown in Table 2. Of 120 PWEs, 89 unvaccinated did not receive the COVID‐19 vaccine (Table 3). Of these 89 unvaccinated PWE, 62 (69.7%) were willing to receive the COVID‐19 vaccine, 25 (28.1%) were unsure about the vaccination, and only 2 patients (2.2%) declined to be vaccinated. Moreover, of the 89 unvaccinated PWE, 67 (75.3%) patients were concerned about worsening seizures, including the frequency of seizures, symptom aggravation, and uncontrollable seizures, and 22 patients (24.7%) were concerned about other adverse reactions. The direct side effects of the COVID‐19 vaccine and the inconvenience in accessing medical services have negatively influenced vaccination intentions.

TABLE 1.

Characteristics of survey participants (n = 120)

Demographic variables	n (%)	Vaccinated (%)	Not yet vaccinated (%)
Age (years)
0 ~ 20	30 (25.00%)	13 (10.83%)	17 (14.17%)
20 ~ 40	69 (57.50%)	22 (18.33%)	47 (39.17%)
>40	21 (17.50%)	6 (5.005)	15 (12.50%)
Gender
Male	66 (55.00%)	15 (12.50%)	51 (42.50)
Female	54 (45.00%)	16 (13.33%)	38 (31.67%)
Level of education
Junior college and above	43 (35.83%)	16 (13.33%)	27 (22.50%)
High school and below	77 (74.17%)	15 (12.50%)	62 (51.67%)
Time of last seizure (month)
Poorly‐controlled group	73 (25.83%)	13 (17.81%)	60 (82.19%)
Well‐controlled group	47 (74.17%)	18 (38.30%)	29 (61.70%)

TABLE 2.

Incidence and composition ratio of adverse reactions after COVID‐19 vaccination in 31 persons with epilepsy

Symptom	Number of occurrences (bout)	Incidence (%)	Composition ratio (%)
Swelling and pain	4	7.69	57.14
Induration	0	0.00	0.00
Rash	0	0.00	0.00
Fever	0	0.00	0.00
Fatigue	2	3.84	28.57
Headache	1	1.92	14.29
Total	7	13.46	100.00

Note: From 2020 to August 31, 2021 epilepsy patients who completed the COVID‐19 vaccination, received a total of 52 doses.

TABLE 3.

Willingness to receive COVID‐19 vaccine and the factors influencing it (scoring: 0 = strongly disagree; 1 = disagree; 2 = agree; 3 = quite agree; 4 = very agree)

Question	n (%)
The willingness to receive COVID‐19 vaccination among unvaccinated PWEs
Yes	62 (69.66%)
No or not yet	27 (30.34%)
The reason why unvaccinated PWEs refuse COVID‐19 vaccine
Worries about epilepsy	67 (75.28%)
Worries about other reasons	22 (24.72%)
The impact of COVID‐19 vaccine on epilepsy
Exacerbate seizures	19 (15.83%)
No effect	14 (11.67%)
Not sure	87 (72.50%)
The impact of epilepsy and ASM on COVID‐19 vaccine
Yes	9 (7.50%)
Not sure	98 (81.67%))
No	13 (10.83%)
Awareness of COVID‐19 vaccine safety (Scoring)
0	1 (0.83%)
1	3 (2.50%)
2	68 (56.67%)
3	22 (18.33%)
4	26 (21.67%)
Awareness of COVID‐19 vaccine effectiveness (Scoring)
0	0 (0.00%)
1	1 (0.83%)
2	74 (61.67%)
3	21 (17.50%)
4	24 (20.00%)

Regarding the safety and effectiveness of the COVID‐19 vaccine, four people chose 0 to 1 point for safety, one chose 0 to 1 point for effectiveness, 68 people (56.67%) chose 2 points for safety, and 74 (61.67%) people choose 2 points for effectiveness. The results for the remaining options are shown in Tables 1 and 2, respectively.

We also conducted an age‐stratified analysis. Most PWE were aged between 25 and 35 years, 36.3%, the largest age group most of the PWE had a high school or below level of education (65%). Furthermore, only 13% had a family history of epilepsy. Taking 6 months as the cutoff, 73 patients experienced one or more epileptic seizures in the past 6 months, and 47 patients had one or more seizures more than 6 months before.

Patient perceptions regarding the safety of the COVID‐19 vaccination are shown in Tables 2 and 4. In this study, 31 PWE had vaccinated against COVID‐19. Of these 31 patients, 13 experienced one or more seizures in the past 6 months, and 18 had seizures more than 6 months ago. Among the vaccinated patients, 6 had symptoms such as local redness, swelling, pain, fatigue, and muscle aches at the inoculation site. Most symptoms appeared during the first injection. Only one of the vaccinated PWE had worsening seizures after the COVID‐19 vaccination (a greater frequency of seizures than that before). Another four PWE could not recall or did not pay attention to the changes in their epilepsy‐related symptoms. The remaining 26 PWE reported no obvious changes in the frequency or severity of seizures after vaccination. On analysing the differences between the 31 vaccinated PWE (Table 4), we did not detect any significant or different features that may have influenced post‐vaccination changes in the patients' seizure outcomes.

TABLE 4.

The influence of COVID‐19 vaccination in PWEs. Analyzed by Fisher's exact test

	N (%)	The impact of COVID‐19 vaccination on seizures of PWEs			P‐value
		Yes	Not	Not sure
Time of last seizure (month)
≤ 6 months	13 (41.94)	1 (3.23)	11 (35.49)	1 (3.23)	.433
> 6 months	18 (58.06)	0 (0)	15 (48.39)	3 (9.68)

Regarding the willingness to be vaccinated, based on our analysis of 89 epilepsy patients who did not receive the COVID‐19 vaccination, we found that the epileptic seizures with 6 months may be one of the reasons for their unwillingness to COVID‐19 vaccination. In contrast, education level and gender did not affect the 89 PWE's willingness to be vaccinated (Table 5).

TABLE 5.

The influence to get COVID‐19 vaccination of the willingness in non‐vaccinated PWE. Analyzed by Fisher's exact test

	N	The willingness to get COVID‐19 vaccination of non‐vaccinated PWE
		Willing	Hesitating	P value
Gender
Male	51	33	18	.241
Female	38	29	9
Education
Junior college and above	27	19	8	.924
High school and below	62	43	19
Time of last seizure (month)
≥6	29	11	18	.000
<6	60	51	9

4. DISCUSSION

The ongoing COVID‐19 pandemic has significantly affected global public health and resulted in a substantial increase in mortality. Furthermore, several deaths continue to occur worldwide. A safe and effective COVID‐19 vaccine is the most effective measure to prevent the spread of the infection. Therefore population immunity is an important public health measure for the prevention of COVID‐19‐related pneumonia. To date, many countries have implemented various COVID‐19 vaccination programs. However, the safety and effectiveness of these vaccines, especially for PWEs remain to be confirmed.

Epilepsy is a common neurological disorder. Studies have confirmed that both objective and subjective pressures can aggravate epileptic seizures in PWE. Objective pressure is an external factor that can induce internal responses in the body. The specific manifestations of objective pressure include infection, high fever, inflammation, brain injury, and other external factors. In recent years, extensive studies have been conducted on the role of the immune system in the etiology of epilepsy. These collective studies have shown that inflammation and epilepsy are involved in the neurological comorbidity of epilepsy. Chronic seizures induce inflammation, which in turn, aggravates the seizures. Moreover proinflammatory signals are generated during seizures. These proinflammatory signals stimulate the activation of inflammatory cells and subsequently lead to the stimulation of inflammatory mediators. Activated inflammatory cells can damage the BBB, which enables the inflammatory mediators to enter the CNS, and consequently, aggravating the epilepsy. Notably, all COVID‐19 vaccines are immunogenic. They activate the humoral and cellular immune systems, to produce antibodies and form an immune memory. Therefore, the safety of COVID‐19 vaccines is of particular importance to PWEs.

In this study, 31 out of 120 PWE (25.8%) were vaccinated. Among the 31 vaccinated PWE, one reported worsening epilepsy, six experienced adverse reactions that were characteristic of the COVID‐19 vaccine, and 26 had no adverse effects. Moreover, there was no significant difference between the 18 well‐controlled and 13 poorly controlled PWEs. From our analyses, only one patient reported worsening epilepsy after the COVID‐19 vaccination, indicating a low probability of adverse effects. Thus, based on our findings, COVID‐19 vaccination is considered safe for PWE. Furthermore, we found that seizure control did not affect post‐vaccination seizure outcomes, which is consistent with previous studies. ¹⁰ Notably, the number of PWE vaccinated in this study was smaller than that in other investigations. ¹¹ , ¹²

Our other goal was to explore the patients' perceptions of COVID‐19 vaccination. There were 89 out of 120 PWE (74.2%) who were not vaccinated. Of the 89 unvaccinated PWE, 69.7% were willing to receive COVID‐19 vaccine and 28.1% were unsure. Only 2.2% were unwilling to be vaccinated. In China, a significant gap in the overall COVID‐19 vaccination willingness has been detected (91.3%). ¹³ For PWE, the main reason for not receiving COVID‐19 vaccination was the fear of worsening epilepsy. Our findings are consistent with those results of previous studies. ¹¹ , ¹⁴

The prevention and treatment of COVID‐19 are a global public health concerns. Vaccination against COVID‐19 provides a population immune barrier that is essential for minimising the risk of COVID‐19‐related pneumonia. A study of the COVID‐19 vaccination among hospital staff (1280 participants) suggested that the incidence of adverse reactions after vaccination was 1.11%. In this study, the reported adverse reactions included local adverse reactions (0.78%) and systemic adverse reactions (1.73%). These results confirmed that the COVID‐19 vaccination available to our PWE demonstrated appropriate safety and efficacy. In our study, the vaccine showed a higher safety factor for PWE. However, our results should be interpreted with caution as our sample size was small. Moreover, patient factors that may have modified the epileptic seizures could not be ruled out. Thus, we cannot definitively ascertain the safety of the COVID‐19 vaccines for PWEs not participated. Based on existing clinical research and related guidelines, we recommend that COVID‐19 vaccines are appropriate for PWE. In the future, clinical research will provide further evidence of the effectiveness and safety of COVID‐19 vaccination in various epileptic populations. Detailed guidelines should be developed for specific patient populations.

This study has some limitations. First, the number of respondents to the questionnaire is not enough to represent the epileptic population. Second, some questions that were not included in the investigation may have influenced the overall findings. Third, our study population was limited to PWE. There is still a lack of research on vaccine hesitancy and adverse reactions following COVID‐19 vaccination in the normal population. Fourth, the questionnaire may have had some defects. Fifth, the questionnaire was distributed by the Department of Neurology of The Third Xiangya Hospital of Central South University through the PWE WeChat group in the hospital or via email. Due to the unknown composition of the WeChat group members, it was impossible to accurately calculate the questionnaire response rate. However, by repeatedly sending the questionnaire QR code, we estimated the response rate to be greater than 60%. Conversely, the questionnaire response rate of those distributed via email was 100%. Furthermore, all participating PWE responded to all items on the questionnaire. As our overall response rate was more than 60%, the survey results were considered valid. Finally, because the questionnaire was sent to patients who attended our outpatient and inpatient departments, the results may be biased. A follow‐up multicenter study with a larger sample size is warranted. More in‐depth statistical analyses with multiple pilots and longer follow‐up are necessary to validate our results.

5. CONCLUSION

The findings from our questionnaire suggest that the COVID‐19 vaccination is safe in PWE, especially in those who are well‐controlled.

CONFLICT OF INTEREST

None.

INFORMED CONSENT

We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Supporting information

Appendix S1

Yang L, He J, Song Z, Zhen W, Chen R, Zhang C, et al. Experiences from COVID‐19 vaccination in patients with epilepsy. Epilepsia Open. 2023;8:307–312. 10.1002/epi4.12667