Association of Seizure with COVID-19 Vaccines in Persons with Epilepsy: A Systematic Review and Meta-analysis (preprint)

Objective: Seizure following immunization, especially in persons with epilepsy (PwE), has long been a concern, and seizure aggravation followed by Coronavirus Disease 2019 (COVID-19) vaccines is a serious issue for PwE. The immunization rate in PwE has been lower compared to same-age controls due to vaccine hesitancy and concerns about seizure control. Herein, we systematically reviewed the seizure activity-related events in PwE following COVID-19 vaccination. Methods: Four search engines were searched from inception until January 31, 2023, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. Random- and fixed-effect models using the logit transformation method were used for meta-analysis. The quality of the studies was evaluated by the Newcastle-Ottawa scale. Outcomes of interest included (a) pooled proportion of increased seizure frequency and (b) pooled incidence proportion of status epilepticus (SE) in PwE receiving COVID-19 vaccines. Results: Of the 2207 studies identified, 18 met eligibility criteria, of which 16 entered the meta-analysis. The pooled proportion of increased seizure frequency (16 studies-4197 PwE) was 5% (95CI: 3%-6%, I2 =57%), further subcategorized into viral vector (3%, 95CI: 2%-7%, I2 =0%), mRNA (5%, 95CI: 4%-7%, I2 =48%), and inactivated (4%, 95CI: 2%-8%, I2 =77%) vaccines. The pooled incidence proportion of SE (15 studies-2480 PwE) was 0.08% (95CI: 0.02%-0.32%, I2 =0%), further subcategorized into the viral vector (0.00%, 95CI: 0.00%-1.00%, I2 =0%), mRNA (0.09%, 95CI: 0.01%-0.62%, I2 =0%), and inactivated (0.00%, 95CI: 0.00%-1.00%, I2 =0%) vaccines. No significant difference was observed between mRNA and viral vector vaccines (5 studies, 1122 vs. 198 PwE, respectively) regarding increased seizure frequency (OR: 1.10, 95CI: 0.49-2.50, p-value=0.81, I2 =0%). Significance: The meta-analysis proposed a 5% increased seizure frequency following COVID-19 vaccination in PwE, with no difference between mRNA and viral vector vaccines. Furthermore, we found a 0.08% incidence proportion for SE. While this safety evidence is noteworthy, this cost should be weighed against vaccination benefits.

Alteration in follow-up echocardiographic indices in patients with COVID-19: a prospective cohort study (preprint)

Background Cardiac problems are frequent (20 to 25%) with COVID-19 and are associated with cardiac complications and in-hospital mortality. Existing research on the echocardiographic examination of COVID-19 focuses mostly on hospitalized patients with severe symptoms and in the acute phase of the disease, leaving out of the spotlight non-hospitalized individuals with mild symptoms. In this study, we wanted to determine the long-term influence of both severe and non-severe COVID-19 on echocardiographic changes. Methods This prospective cohort study was conducted during Iran's third COVID-19 wave in November 2020 among healthcare workers with a history of COVID-19 but otherwise healthy. Initially, a total of 100 patients underwent the primary echocardiographic examination 6 to 8 weeks following COVID-19 onset, and 6 months after the COVID-19 diagnosis, 64 subjects underwent the secondary echocardiographic evaluations. Based on clinical or radiological evidence, individuals were categorized into two groups of non-severe and severe COVID-19. Results Of 64 participants, 42 (65.6%) were women. The patients ' mean age was 40.4±8.1 years. In the non-severe COVID-19 group, among left ventricular (LV) echocardiographic indices, stroke volume index and ejection fraction increased significantly (24.7±4.1 cc/m2 vs. 29.7±7.0 cc/m2, p-value<0.001 and 61.9% [59.8-64.5] vs. 63.8% [58.2-68.9], p-value=0.029, respectively). Among right ventricular indices, free-wall global longitudinal strain decreased significantly in the secondary echocardiogram: (-32.3±4.6% vs. -28.8±5.8%, p-value=0.002). In the severe COVID-19 group, from LV echocardiographic indices, global longitudinal strain increased significantly over the follow-up period (-20% [-21.4- -19] vs. -23.9% [-25.3--21.9], p-value=0.004) and from RV indices, the fractional area change showed a significant decrease (47.2% [42.3-52.2] vs. 36.4% [31.1-45], p-value=0.002). Conclusion Although some patterns of significant change were seen among echocardiographic indices, COVID-19, regardless of severity, did not lead to cardiac impairment in an otherwise healthy population. The current results may not present the outcomes of older adults or with a history of cardiac problems against COVID-19.

Bell's Palsy Following SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis (preprint)

Background and Objective Bell's palsy (BP) has been considered as a serious adverse event following the SARS-CoV-2 vaccination. Many studies have reported BP following vaccination, although neither a causative relationship nor a prevalence of the condition higher than the general population has been established. The outcomes of interest were to compare BP incidence among (a) SARS-CoV-2 vaccine recipients, (b) nonrecipients in the placebo or unvaccinated cohorts, (c) different types of SARS-CoV-2 vaccines, and (d) SARS-CoV-2 infected vs. SARS-CoV-2 vaccinated individuals. Methods We performed a systematic search through MEDLINE (via PubMed), Web of Science, Scopus, Cochrane library, and Google Scholar from the inception to August 15, 2022. We included articles reporting individuals receiving any SARS-CoV-2 vaccine in whom BP had occurred. Studies reporting facial paralysis due to etiologies other than BP were excluded. Random- and fixed-effects meta-analyses using the Mantel-Haenszel method were conducted for the quantitative synthesis. Newcastle-Ottawa scale (NOS) was used to assess the quality. The study was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, and the protocol was registered with PROSPERO (CRD42022313299). Analyses were carried out using the R, version 4.2.1 (R package 'meta' version 5.2-0). Results Fifty studies were included, of which 17 entered the quantitative synthesis. First, pooling four phase-3 randomized controlled trials (RCT) indicated BP occurrence was significantly higher in SARS-CoV-2 vaccines (77, 525 doses) compared to placebo (66, 682 doses) (OR = 3.00, 95% CI = 1.10 - 8.18, I2 = 0%). Second, pooling nine observational studies of mRNA SARS-CoV-2 vaccine doses (13, 518,026) and matched unvaccinated individuals (13, 510,701) revealed no significant increase in the odds of BP in the vaccinated group compared to the unvaccinated group (OR: 0.70 (95% CI 0.42-1.16), I2=94%). The third meta-analysis suggested that post-vaccination BP among first dose Pfizer/BioNTech recipients (22,760,698) did not significantly differ from that in first dose Oxford/AstraZeneca recipients (22,978,880) (OR = 0.97, 95% CI = 0.82 - 1.15, I2 = 0%). According to the fourth meta-analysis, BP was significantly more commonly reported after SARS-CoV-2 infection (2,641,398) than after SARS-CoV-2 vaccinations (36,988,718) (RR = 4.03, 95% CI = 1.78 - 9.12, I2 = 96%). Conclusion Our meta-analysis suggests a higher incidence of BP among vaccinated vs. placebo groups. BP occurrence did not significantly differ between Pfizer/BioNTech and Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccines.

Alternation in follow-up echocardiographic indices in patients with COVID-19: a prospective cohort study (preprint)

Background: Cardiovascular complications are frequently reported among patients with pulmonary coronavirus disease 2019 (COVID-19) infection. Echocardiography has been immensely implemented for diagnosing cardiovascular involvements. We aimed to evaluate the changes in echocardiographic parameters in health care workers infected with COVID-19 during follow-up. Methods: This prospective study was conducted during Iran’s third COVID-19 wave in November 2020 among health care workers who were infected with COVID-19 but otherwise healthy. A total of 100 patients underwent echocardiographic examination six to eight weeks following recovery, an early follow-up. Six months after the COVID-19 diagnosis, as the late follow-up, 63 subjects underwent echocardiographic evaluations. Moreover, based on clinical and radiological evidence, individuals were categorized into two groups of non-severe and severe COVID-19. Results: The participants’ mean age was 40.4±8.1 years. In the non-severe COVID-19 group, Right Ventricle Free-Wall Global Longitudinal Strain (RVFWGLS) significantly decreased in the follow-up echocardiogram (-32.3±4.6% vs. -28.8±5.8%, p-value=0.002). RV Fraction Area Change (RV-FAC) (46.6% [43.6-53] vs. 39.7% [25-43] , p-value <0.001) and, Tricuspid Annular Plane Systolic Excursion (TAPSE) (21 mm [19-24] vs. 23 mm [20-25], p-value=0.09) did not show a significant change. In the severe COVID-19 group in late echocardiogram, RVFWGLS showed no statistically significant change (-28.3%±3.5 vs. -28.6%±5.1, p-value=0.79). The RV-FAC (47.2% [42.3-52.2] vs. 36.4% [31.1-45], p-value=0.002) showed a significant decrease, and TAPSE (22.5 mm [19.1-24.2] vs. 23 mm [21-25], p-value= 0.55) was comparable. Conclusion: Although LV and RV functions did not vary significantly over time in our entire cohort, different patterns of changes were discovered according to baseline function.