Pharmacotherapy for SARS-CoV-2 and Seizures for Drug Repurposing Presumed on Mechanistic Targets.

The currently circulating novel SARS-CoV-2 coronavirus disease (COVID-19) has brought the whole world to a standstill. Recent studies have deciphered the viral genome structure, epidemiology and are in the process of unveiling multiple mechanisms of pathogenesis. Apart from atypical pneumonia and lung disease manifestations, this disease has also been found to be associated with neurological symptoms, which include dizziness, headache, stroke, or seizures, among others. However, a possible direct or indirect association between SARS-CoV-2 and seizures is still not clear. In any manner, it may be of interest to analyze the drugs being used for viral infection in the background of epilepsy or vice versa. To identify the most credible drug candidate for COVID-19 in persons with epilepsy or COVID-19 patients experiencing seizures. A literature search for original and review articles was performed, and further, the Comparative Toxicogenomics Database was used to unearth the most credible drug candidate. Our search based on common mechanistic targets affecting SARS-CoV-2 and seizures revealed ivermectin, dexamethasone, anakinra, and tocilizumab for protection against both COVID-19 and seizures. Amongst the antiseizure medications, we found valproic acid as the most probable pharmacotherapy for COVID-19 patients experiencing seizures. These findings would hopefully provide the basis for initiating further studies on the pathogenesis and drug targeting strategies for this emerging infection accompanied with seizures or in people with epilepsy.

COVID-19 prevalence and mortality in people with epilepsy: A nation-wide multicenter study.

BACKGROUND: To assess the prevalence, severity, and mortality of COVID-19 in people with epilepsy (PWE) and evaluate seizure control in PWE during and after COVID-19. METHODS: Retrospective, observational, multicenter study conducted in 14 hospitals. Medical records of randomly selected PWE followed at neurology outpatient clinics were reviewed. Proportion of PWE with a positive test for SARS-CoV-2 during 2020 was calculated. Risk factors associated with COVID-19 and its morbimortality were evaluated. RESULTS: 2751 PWE were included, mean age 48.8 years (18-99), 72.4% had focal epilepsy, and 35% were drug-refractory. COVID-19 prevalence in PWE was 5.53%, while in the Spanish population was 4.26%. Proportion of admissions to hospital, ICU, and deaths in PWE were 17.1%, 2%, and 4.61% of COVID-19 cases, while in Spanish population were 10.81%, 0.95%, and 2.57%, respectively. A severe form of COVID-19 occurred in 11.8%; dyslipidemia, institutionalization at long-term care facilities, intellectual disability, and older age were associated risk factors. Older age, hypertension, dyslipidemia, cardiac disease, and institutionalization were associated with mortality from COVID-19. Seizure control was stable in 90.1% of PWE during acute COVID-19, while 8.6% reported an increase in seizure frequency. During post-COVID-19 follow-up, 4.6% reported seizure control worsening. CONCLUSIONS: COVID-19 was moderately prevalent in PWE. One out of 5 patients required medical attention and 4.6% died due to COVID-19. Older age, dyslipidemia, institutionalization, and intellectual disability were significant risk factors associated with severe COVID-19. Seizure control remained stable during COVID-19 and throughout long-term follow-up in most PWE who contracted the infection.

Gene therapies and COVID-19 vaccines: a necessary discussion in relation with viral vector-based approaches.

The COVID-19 pandemic is adding an unanticipated concern for those affected by genetic diseases. Most of the new treatment achievements for these patients are made possible as a result of advances in viral-based products. Among them, adenoviruses (AdV) and especially adeno-associated viruses (AAV) are important players. The concerns and the conversation around this issue have increased as COVID-19 vaccines approach the market. What if the viral vectors become the mainstream strategy for vaccine development? Will the immune response elicited against the vector compromise the efficacy of future gene therapies? Patients with genetic diseases and patient advocacy groups are requesting information to the medical community about the potential impact of these vaccines in future gene therapy treatments, and physicians and scientists are not able to provide satisfactory answer yet. Importantly, the frequency of cross-reactivity among different AAV serotypes can be as high as 50%. This would have potential implications for patients with genetic disorders who could benefit from gene therapies, often coming in the form of AAV-based gene therapies. As in many other aspects, this pandemic is challenging our capacity to coordinate, plan ahead and align different medical objectives. In this case, having such conversation early on might allow us to make the right choices while we are still on time.