A review of neurological side effects of COVID-19 vaccination.

Following the COVID-19 virus epidemic, extensive, coordinated international research has led to the rapid development of effective vaccines. Although vaccines are now considered the best way to achieve collective safety and control mortality, due to the critical situation, these vaccines have been issued the emergency use licenses and some of their potential subsequence side effects have been overlooked. At the same time, there are many reports of side effects after getting a COVID-19 vaccine. According to these reports, vaccination can have an adverse event, especially on nervous system. The most important and common complications are cerebrovascular disorders including cerebral venous sinus thrombosis, transient ischemic attack, intracerebral hemorrhage, ischemic stroke, and demyelinating disorders including transverse myelitis, first manifestation of MS, and neuromyelitis optica. These effects are often acute and transient, but they can be severe and even fatal in a few cases. Herein, we have provided a comprehensive review of documents reporting neurological side effects of COVID-19 vaccines in international databases from 2020 to 2022 and discussed neurological disorders possibly caused by vaccination.

Neuromodulation by selective angiotensin-converting enzyme 2 inhibitors.

Here, neuromodulatory effects of selective angiotensin-converting enzyme 2 (ACE2) inhibitors were investigated. Two different types of small molecule ligands for ACE2 inhibition were selected using chemical genetic approach, they were synthesized using developed chemical method and tested using presynaptic rat brain nerve terminals (synaptosomes). EBC-36032 (1 µM) increased in a dose-dependent manner spontaneous and stimulated ROS generation in nerve terminals that was of non-mitochondrial origin. Another inhibitor EBC-36033 (MLN-4760) was inert regarding modulation of ROS generation. EBC-36032 and EBC-36033 (100 µM) did not modulate the exocytotic release of L-[14C]glutamate, whereas both inhibitors decreased the initial rate of uptake, but not accumulation (10 min) of L-[14C]glutamate by nerve terminals. EBC-36032 (100 µM) decreased the exocytotic release as well as the initial rate and accumulation of [3H]GABA by nerve terminals. EBC-36032 and EBC-36033 did not change the extracellular levels and transporter-mediated release of [3H]GABA and L-[14C]glutamate, and tonic leakage of [3H]GABA from nerve terminals. Therefore, synthesized selective ACE2 inhibitors decreased uptake of glutamate and GABA as well as exocytosis of GABA at the presynaptic level. The initial rate of glutamate uptake was the only parameter that was mitigated by both ACE2 inhibitors despite stereochemistry issues. In terms of ACE2-targeted antiviral/anti-SARS-CoV-2 and other therapies, novel ACE2 inhibitors should be checked on the subject of possible renin-angiotensin system (RAS)-independent neurological side effects.

Small Fiber Neuropathy Associated With the Moderna SARS-CoV-2 Vaccine.

Efforts of controlling viral transmission began soon after the first cases of coronavirus disease 2019 (COVID-19) infections were identified. Initial efforts were related to contact precautions, hand hygiene, and mask-wearing; however, it was soon evident that a robust global immunization drive was the most effective way to curb disease transmission. In the United States, the first doses of COVID-19 vaccines were rolled out soon after the FDA granted emergency use authorization for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. What this also meant was that many of the routine phases that any new drug or vaccine goes through before being released publicly were bypassed. Over the past two years, various side effects and reactions have been seen after COVID-19 vaccine administration, the most common being local injection site events (e.g., pain, redness, swelling) and systemic effects (e.g., fatigue, headaches, myalgias). We report the case of a 64-year-old female who developed bilateral lower extremity numbness and tingling within weeks of receiving the third dose of Moderna SARS-CoV-2 vaccine. The patient underwent extensive testing to ascertain the diagnosis. She had negative autonomic testing and normal nerve conduction study/electromyography (EMG), which did not reveal large fiber neuropathy. Eventually, the patient underwent a skin biopsy, which revealed small fiber neuropathy. This case report highlights the importance of keeping a broad differential for rare side effects, such as small fiber neuropathy, that are currently being seen and reported in the literature.

Neurological Conditions Following COVID-19 Vaccinations: Chance or Association?

Coronavirus disease 2019 (COVID-19) has been labeled a global pandemic with the first reported case of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurring in Wuhan, China in December 2019. To combat the alarming, increasing rate of those affected by the virus, vaccine development ensued. As mass vaccination initiatives against COVID-19 ensued, adverse reactions began emerging. This non-consecutive, population-based case series focuses on four vaccine-associated neurological adverse events across the central and peripheral nervous system detailing the diagnosis, treatment and subsequent follow-up management. These four patients presented to public and private hospitals in Trinidad and Tobago with new-onset neurological diseases soon after their first doses of a COVID-19 vaccine: two after the Pfizer-BioNTech vaccine (one case of new-onset seizures and one case of longitudinally extensive transverse myelitis) and two after the ChAdOx1 nCoV-19 vaccine (one case of Guillain-Barre syndrome and one case of meningitis-retention syndrome). The background incidence rates of neurological conditions in the population and the large numbers of persons being vaccinated means that some of these conditions will appear in the post-vaccination window by chance. Hence, establishing causal links is difficult. The close temporal relationship between vaccination and the presenting symptoms, the biological plausibility, and the extensive diagnostic workup to exclude other causes fulfill criteria provided by the World Health Organization for causality assessment of an adverse event following immunization on an individual level. On this basis, it was determined that these adverse events were likely due to the vaccines. However, establishing causal links on a population level requires large epidemiological studies and cannot be done on individual case reports alone. While physicians should be cognizant of even these rare adverse events of vaccines, it should be reiterated that the overall safety profile of vaccines is well established.