ABSTRACT
Ivermectin is a well-known and widely used anti-parasitic drug. Recently, in vitro data suggest anti-viral efficacy of the drug, albeit at much higher concentrations than currently approved. Despite warnings by several governing bodies, the (uncontrolled) human use of ivermectin has significantly increased during the COVID-19 epidemic. This study thus aimed to elucidate potential neurological risk of particularly the veterinary formulation of ivermectin in comparison to pure ivermectin. Zebrafish eggs (1hpf) and larvae (4dpf) were exposed to a range of concentrations of either pure ivermectin (IVM) or a veterinary formulation (V-IVM) for a period of 24 hours. Behavioral responses to both treatments were assessed at various timepoints using the pentylenetetrazol assay, the light-dark assay and a 5-day teratogenesis protocol. In addition, dissolution rates were calculated for both treatments. Acute responses of larvae at 4 - <5dpf was similar for both treatments – a transient hyperlocomotion was followed by a general hypolocomotion (ANOVA dose effect, P<0.01). Both IVM and V-IVM-treated larvae showed significant dose-dependent (ANOVA dose effect, P<0.0001) decreases in responsiveness to repeated light-dark transitions, which again was more pronounced in IVM. These effects were maintained after 24 hours of exposure. In contrast, when ivermectin was administered prior to establishment of the blood brain-barrier in the teratogenesis protocol, V-IVM treatment was linked to more severe activity decline on <5dpf. Differences in dissolution rates cannot account for these differences. In conclusion, current data suggest significantly higher neurological risk of a veterinary formulation of ivermectin under conditions of penetration across the blood brain-barrier.
ABSTRACT
Background: In late 2019, Coronavirus disease 2019 has been declared as a global emergency by World Health Organization. Hopefully, recent reports of effective and safe vaccines were welcomed, and approved on emergency base. Millions of recipients had received one of the approved COVID 19 vaccines, with lots of adverse events recorded global wide. Objective: To assess post-COVID vaccination immune-mediated adverse events and evaluate its association to specific type of vaccine global wide. Methods: Systematic literature review and meta-analysis of published reports (since December 2020 till December 2021) on immune-mediated adverse events post-COVID vaccination. Results: We evaluated 34 published studies; 460 cases with various adverse events post-COVID vaccination. Studies in current literature are primarily retrospective case series, isolated case reports or narrative studies. Different COVID vaccines were involved. Results' data was subcategorized according to associated vaccine. Adverse effects of COVID-19 vaccinations included thrombotic, neurological, myocarditis, ocular, dermatological, renal, hematological events timely linked to inoculation. Each vaccine type was linked to adverse profile that differ from others. Conclusion: High suspicion of post-vaccination adverse events is mandatory to provoke earlier detection, better understanding, optimum prevention, and management. Specific vaccine/patient risk profile is needed to selectively categorize target population to reduce morbidity and mortality post-vaccination.