Safety and Tolerability of COVID-19 Vaccine in Children With Epilepsy: A Prospective, Multicenter Study.

BACKGROUND: We designed this study to investigate the effects of the coronavirus disease 2019 (COVID-19) vaccine on epileptic seizures, as well as its adverse effects, in children with epilepsy (<18 years). METHODS: This anonymous questionnaire study involved a multicenter prospective survey of outpatients and inpatients with epilepsy (＜18 years) registered in epilepsy clinics in eight hospitals in six cities of Shandong Province. RESULTS: A total of 224 children with epilepsy were included in the study. Fifty of them experienced general adverse events after vaccination. The most common local adverse events were pain or tenderness at the injection site. The most common systemic adverse effects were muscle soreness and headache. No severe adverse events were reported. There were no significant differences in the number of antiseizure medications (P = 0.459), gender (P = 0.336), etiology (P = 0.449), age (P = 0.499), duration of disease (P = 0.546), or seizure type (P = 0.475) between the patients with and without general adverse events. We found that the risk of seizure after vaccination was decreased in children who were seizure free for more than six months before vaccination. There was no significant difference in the number of seizures during the first month before vaccination, the first month after the first dose, and the first month after the second dose (P = 0.091). CONCLUSION: The benefits of vaccination against COVID-19 outweighed the risks of seizures/relapses and severe adverse events after vaccination for children with epilepsy.

Effect of inactivated COVID-19 vaccines on seizure frequency in patients with epilepsy: A multicenter, prospective study.

Objectives: Several COVID-19 vaccines list "uncontrolled epilepsy" as a contraindication for vaccination. This consequently restricts vaccination against COVID-19 in patients with epilepsy (PWE). However, there is no strong evidence that COVID-19 vaccination can exacerbate conditions in PWE. This study aims to determine the impact of COVID-19 vaccination on PWE. Methods: PWE were prospectively recruited from 25 epilepsy centers. We recorded the seizure frequency at three time periods (one month before the first vaccination and one month after the first and second vaccinations). A generalized linear mixed-effects model (GLMM) was used for analysis, and the adjusted incidence rate ratio (AIRR) with 95% CI was presented and interpreted accordingly. Results: Overall, 859 PWE were included in the analysis. Thirty-one (3.6%) and 35 (4.1%) patients were found to have increased seizure frequency after the two doses, respectively. Age had an interaction with time. The seizure frequency in adults decreased by 81% after the first dose (AIRR=0.19, 95% CI:0.11-0.34) and 85% after the second dose (AIRR=0.16, 95% CI:0.08-0.30). In juveniles (<18), it was 25% (AIRR=0.75, 95% CI:0.42-1.34) and 51% (AIRR=0.49, 95% CI:0.25-0.95), respectively. Interval between the last seizure before vaccination and the first dose of vaccination (ILSFV) had a significant effect on seizure frequency after vaccination. Seizure frequency in PWE with hereditary epilepsy after vaccination was significantly higher than that in PWE with unknown etiology (AIRR=1.95, 95% CI: 1.17-3.24). Two hundred and seventeen (25.3%) patients experienced non-epileptic but not serious adverse reactions. Discussion: The inactivated COVID-19 vaccine does not significantly increase seizure frequency in PWE. The limitations of vaccination in PWE should focus on aspects other than control status. Juvenile PWE should be of greater concern after vaccination because they have lower safety. Finally, PWE should not reduce the dosage of anti-seizure medication during the peri-vaccination period.

Safety and tolerability of COVID-19 vaccine in children with epilepsy: a prospective, multicenter study

Introduction We designed this study to investigate the effects of the coronavirus disease 2019 (COVID-19) vaccine on epileptic seizures, as well as its adverse effects, in children with epilepsy (< 18 years). Methods This anonymous questionnaire study involved a multicenter prospective survey of outpatients and inpatients with epilepsy (＜18 years) registered in epilepsy clinics in 8 hospitals in six cities of Shandong Province. Results A total of 224 children with epilepsy were included in the study. Fifty of them experienced general adverse events after vaccination. The most common local adverse events were pain or tenderness at the injection site. The most common systemic adverse effects were muscle soreness and headache. No severe adverse events were reported. There were no significant differences in the number of anti-seizure medications (ASMs) (P =0.459), gender (P =0.336), etiology (P =0.449), age (P =0.499), duration of disease (P =0.546) or seizure type (P =0.475) between the patients with and without general adverse events. We found that the risk of seizure after vaccination was decreased in children who were seizure-free for more than 6 months before vaccination. There was no significant difference in the number of seizures during the first month before vaccination, the first month after the first dose and the first month after the second dose (P = 0.091). Conclusion The benefits of vaccination against COVID-19 outweighed the risks of seizures/relapses and severe adverse events after vaccination for children with epilepsy.

Oral IRAK4 inhibitor BAY-1834845 prevents acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a lethal clinical entity that has become an emergency event with the outbreak of COVID-19. However, to date, there are no well-proven pharmacotherapies except dexamethasone. This study is aimed to evaluate IRAK4 inhibitors as a potential treatment for ARDS-cytokine release syndrome (CRS). We applied two IRAK4 inhibitors, BAY-1834845 and PF-06650833 to an inhaled lipopolysaccharide (LPS)-induced ARDS mouse model with control of high dose dexamethasone (10 mg/kg). Unexpectedly, although both compounds had excellent IC50 on IRAK4 kinase activity, only BAY-1834845 but not PF-06650833 or high dose dexamethasone could significantly prevent lung injury according to a blinded pathology scoring. Further, only BAY-1834845 and BAY-1834845 combined with dexamethasone could effectively improve the injury score of pre-existed ARDS. Compared with PF-06650833 and high dose dexamethasone, BAY-1834845 remarkably decreased inflammatory cells infiltrating lung tissue and neutrophil count in BALF. BAY-1834845, DEX, and the combination of the two agents could decrease BALF total T cells, monocyte, and macrophages. In further cell type enrichment analysis based on lung tissue RNA-seq, both BAY-1834845 and dexamethasone decreased signatures of inflammatory cells and effector lymphocytes. Interestingly, unlike the dexamethasone group, BAY-1834845 largely preserved the signatures of naïve lymphocytes and stromal cells such as endothelial cells, chondrocytes, and smooth muscle cells. Differential gene enrichment suggested that BAY-1834845 downregulated genes more efficiently than dexamethasone, especially TNF, IL-17, interferon, and Toll-like receptor signaling.

A three-arm, multicenter, open-label randomized controlled trial of hydroxychloroquine and low-dose prednisone to treat recurrent pregnancy loss in women with undifferentiated connective tissue diseases: protocol for the Immunosuppressant regimens for LIving FEtuses (ILIFE) trial.

BACKGROUND: Undifferentiated connective tissue disease (UCTD) is known to induce adverse pregnancy outcomes and even recurrent spontaneous abortion (RSA) by placental vascular damage and inflammation activation. Anticoagulation can prevent pregnancy morbidities. However, it is unknown whether the addition of immune suppressants to anticoagulation can prevent spontaneous pregnancy loss in UCTD patients. The purpose of this study is to evaluate the efficacy of hydroxychloroquine (HCQ) and low-dose prednisone on recurrent pregnancy loss for women with UCTD. METHODS: The Immunosuppressant for Living Fetuses (ILIFE) Trial is a three-arm, multicenter, open-label randomized controlled trial with the primary objective of comparing hydroxychloroquine combined with low-dose prednisone and anticoagulation with anticoagulation alone in treating UCTD women with recurrent spontaneous abortion. The third arm of using hydroxychloroquine combined with anticoagulant for secondary comparison. A total of 426 eligible patients will be randomly assigned to each of the three arms with a 1:1:1 allocation ratio. The primary outcome is the rate of live births. Secondary outcomes include adverse pregnancy outcomes and progression of UCTD. DISCUSSION: This is the first multi-center, open-label, randomized controlled trial which evaluates the efficacy of immunosuppressant regimens on pregnancy outcomes and UCTD progression. It will provide evidence on whether the immunosuppressant ameliorates the pregnancy prognosis in UCTD patients with RSA and the progression into defined connective tissue disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03671174 . Registered on 14 September 2018.