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.

Management of COVID-19 in patients with seizures: Mechanisms of action of potential COVID-19 drug treatments and consideration for potential drug-drug interactions with anti-seizure medications.

In regard to the global pandemic of COVID-19, it seems that persons with epilepsy (PWE) are not more vulnerable to get infected by SARS-CoV-2, nor are they more susceptible to a critical course of the disease. However, management of acute seizures in patients with COVID-19 as well as management of PWE and COVID-19 needs to consider potential drug-drug interactions between antiseizure drugs and candidate drugs currently assessed as therapeutic options for COVID-19. Repurposing of several licensed and investigational drugs is discussed for therapeutic management of COVID-19. While for none of these approaches, efficacy and tolerability has been confirmed yet in sufficiently powered and controlled clinical studies, testing is ongoing with multiple clinical trials worldwide. Here, we have summarized the possible mechanisms of action of drugs currently considered as potential therapeutic options for COVID-19 management along with possible and confirmed drug-drug interactions that should be considered for a combination of antiseizure drugs and COVID-19 candidate drugs. Our review suggests that potential drug-drug interactions should be taken into account with drugs such as chloroquine/hydroxychloroquine and lopinavir/ritonavir while remdesivir and tocilizumab may be less prone to clinically relevant interactions with ASMs.

COVID-19 and seizures: Is there a link?

The rapid spread of the SARS-CoV-2 pandemic poses particular challenges to the management of persons with chronic disease. Reports of a possible neuroinvasiveness of SARS-CoV-2 as well as pathophysiological mechanisms and indirect consequences in severe COVID-19 cases raise the question of whether the infection can be associated with an increased risk of seizure recurrence or the development of new onset and acute symptomatic seizures. Although the literature does not provide relevant evidence for seizure worsening in persons with epilepsy during the course of a SARS-CoV-2 infection, there are theoretical risks, for example, seizures triggered by fever. Moreover, a severe disease course and advanced disease stages can, for instance, result in hypoxic encephalopathy, cerebrovascular events, and cytokine storm, which may trigger the development of acute seizures. This is further confirmed by reports of occasional seizures in COVID-19 patients. Although the low number of reports so far suggests that the risk may be relatively low, the reports indicate that an early neurological manifestation with seizures should not be ruled out. In the context of these cases, we discuss possible pathophysiological mechanisms that may trigger ictogenesis in patients with SARS-CoV-2 infection.