SARS-CoV-2 Vaccines Show No Increased Risk for New-Onset Seizures

Ali Rafati, MD

In a recently published review and meta-analysis of more than 118,000 participants in randomized clinical trials (RCTs), results showed that the incidence of new-onset seizure was not significantly different between SARS-CoV-2 vaccine recipients and those given placebo.

Of 3065 recorded identified through the systemic database search, after title, abstract, and full-text screening, 6 studies were included in the qualitative and quantitative synethesis. During the 28-day follow-up period after each vaccine/placebo, the pooled analysis of RCTs revealed an OR of 2.70 (95% CI, 0.76-9.57; P = .12; I² = 0%; τ2 = 0, Cochran Q P = .74) for seizure incidence; however, the difference between the 2 groups was not statistically significant (vaccine: 9 of 63,521 events [0.014%]; placebo: 1 of 54,919 events [0.002%]).

In subgroup analyses, there was no significant difference in terms of new-onset seizure incidence for adults receiving viral vector vaccines (vs placebo; OR, 3.63; 95% CI, 0.60-22.00; I² = 14%, τ2 = 0, Cochran Q P = .28) and children receiving viral vector vaccines (vs placebo; OR, 1.00; 95% CI, 0.10-9.61; I² = 0%, τ2 = 0, Cochran Q P > .99) during the 28-day follow-up period. The X² test for subgroup differences showed no statistically significant difference among subgroups (P = .61).

"The pathogenesis of postimmunization seizures occurrence is not clearly determined,” lead author Ali Rafati, MD, postdoctoral researcher at the Iran School of Medicine, and colleagues, wrote. "Also, among the included studies, the majority did not suggest a suspected pathophysiology for postvaccination seizure occurrence. The SARS-CoV-2 vaccines set off a series of events that could result in the release of inflammatory and proinflammatory molecules, triggering neuronal hyperexcitability and seizures."

They added, "Indeed, seizures could be caused by induction of glutamate release and inhibition of the release of inhibitory neurotransmitters, triggered by proinflammatory cytokines in the brain, as also happens in SARS-CoV-2 infection. Furthermore, SARS-CoV-2 vaccines could result in autoimmune encephalopathy, which is commonly associated with seizures."

Three RCTs studies reported the results of the entire double-blinded phase (until unmasking), the interim 28-day follow-up results of which were previously published for 2 of them. These studies, which had a median follow-up of 148 days (IQR, 131-162), 121 days (range, 1-284), and 43 days (range, 36-48), assessed the safety and efficacy of the Moderna vaccine, Janssen vaccine, and CoronaVac vaccine, respectively. After pooling all 3, no statistical difference was identified between the vaccine and placebo groups (vaccine: 13 of 43,724 events [0.03%]; placebo: 5 of 40,612 events [0.012%]; OR, 2.31; 95% CI, 0.86-3.23; P > .99, I² = 0%, τ2 = 0, Cochran Q P = .95).

READ MORE: Diazepam Buccal Film’s Role in Treating Intermittent Pediatric Seizures, with Michael Rogawski, MD, PhD

Investigators also conduced pooled analyses on other neurological adverse events (AEs) from RCT data to ensure that the absence of difference regarding new-onset seizures between the vaccine and placebo groups is not because of poor and improper capturing of AEs. Overall, 3 studies reported ischemic stroke and syncope, and 4 studies reported severe headaches in a 28-day follow-up period.

Overall, the results showed no significant difference in the incidence of ischemic stroke between the vaccine and placebo groups (vaccine: 4 events [0.008%]; placebo: 0 events; OR, 3.64; 95% CI, 0.60-22.11; P = .16; I² = 0%, τ2 = 0, Cochran Q P = .96). Similarly, no statistically significant difference was identified between the groups regarding severe headache (vaccine: 15 events [0.034%]; placebo: 11 [0.028%]; OR, 1.16; 95% CI, 0.54-2.50; P = .70, I² = 0%, τ2 = 0, Cochran Q P = .75).

"Similar to SARS-CoV-2, seizures can also occur following non–SARS-CoV-2 vaccination, such as diphtheria, measles, mumps, DTP, DTaP-IPV-Hib, and MMR, which might be due to the induced inflammation and fever," Rafati et al wrote. "However, follow-up analyses revealed that these vaccines did not put the recipients at elevated risk for developing seizures in the long term. Overall, the pathological mechanisms for vaccine-induced seizures in SARS-CoV-2 and non–SARS-CoV-2 could share similarities, which could be an interesting area for future research."

REFERENCE
1. Rafati A, Jameie M, Amanollahi M, et al. Association of new-onset seizures with SARS-CoV-2 vaccines: a systematic review and meta-analysis of randomized clinical trials. JAMA Neurol. Published online April 29, 2024. doi:10.1001/jamaneurol.2024.0967