NEUROPHYSIOLOGICAL ASSESSMENT OF SPEECH FUNCTION IN INDIVIDUALS HAVING A HISTORY OF MILD COVID-19

Establishing a link between the objective research data and the thought process is one of the major issues of modern neurophysiology. The study was aimed to find an opportunity to perform objective analysis of the causes of cognitive impairment in individuals having a history of mild novel coronavirus infection by solving the inverse EEG problem. A total of 38 COVID-19 survivors were assessed, who had returned to work. The control group included 33 healthy individuals. EEG was recorded using a 128-channel system with an average reference. The data obtained were subjected to the EEG microstate segmentation and converted using the algorithm for solving the inverse EEG problem implemented in the sLORETA software package. In individuals with no history of COVID-19 being in a state of relaxed wakefulness, the component of rhythmic activity within Brodmann area 47, responsible for perception and realization of music, was found in all classes of EEG microstates (0.01 < p < 0.05;χ2-test). Auditory-speech load was characterized by rhythmic activity within areas 22, 23, 37, 39, 40, 44, 45, and 47. In individuals having a history of novel coronavirus infection being in a state of relaxed wakefulness, rhythmic activity within areas 22, 37, 39, 40 was detected. Under auditory-speech load, there was rhythmic activity within areas 37, 39, and 41 (p < 0.05;χ2-test). Thus, alterations in realization of speech function in the form of the disordered sequence of switching on the main language centers were revealed in COVID-19 survivors. © 2022 Federal Medical Biological Agency Publishing Group. All Rights Reserved.

EEG Microstate Analysis and the EEG Inverse Problem Solution as a Tool for Diagnosing Cognitive Dysfunctions in Individuals Who Have Had a Mild Form of COVID-19

The term “postcovid syndrome” is firmly entrenched in medical terminology, however, many aspects of its clinical manifestations are not well understood. The aim of this work was to find the causes of the development of cognitive dysfunctions in individuals who had a mild form of SARS-CoV-2 using high-density EEG technology and solving an inverse neurophysiological problem. A dynamic study was conducted of 38 people who had COVID-19 and returned to work. Neurophysiological studies were carried out using the EGI-GES-300 system (128 channels). The descriptive characteristics of electroencephalograms were built on the method of studying the spectral density of the EEG signal on the surface of the scalp, and the dynamic characteristics of the signal were studied by fixing EEG microstates, using the method of D. Lehmann and T. Koenig (2018). In the study, a relatively new diagnostic technique for studying cognitive impairments based on the analysis of EEG microstates was implemented, which made it possible to identify signs of functional restructuring of the neuronal macronetworks of the brain and trace the characteristic adaptation of a person during the period of convalescence. The results obtained made it possible to detect a violation of the implementation of the speech function, as a violation of the perception system (ventral information flow system), as well as the connection between the fields of Wernicke’s center and Broca’s center (dorsal information flow system), leading to the development of communicative dysfunctions that cause characteristic clinical symptoms due to impaired perception of new information and difficulties in implementing the solution. Thus, the survey showed that SARS-Co-V2 causes objective changes in the functional activity of the brain, which are manifested by the syndrome of cognitive dysfunction and require the development of more sensitive clinical tests than currently used.

Preclinical Studies of Immunogenity, Protectivity, and Safety of the Combined Vector Vaccine for Prevention of the Middle East Respiratory Syndrome.

The Middle East Respiratory Syndrome (MERS) is an acute inflammatory disease of the respiratory system caused by the MERS-CoV coronavirus. The mortality rate for MERS is about 34.5%. Due to its high mortality rate, the lack of therapeutic and prophylactic agents, and the continuing threat of the spread of MERS beyond its current confines, developing a vaccine is a pressing task, because vaccination would help limit the spread of MERS and reduce its death toll. We have developed a combined vector vaccine for the prevention of MERS based on recombinant human adenovirus serotypes 26 and 5. Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. Studies of the cellular immune response in mice after vaccination showed the emergence of a specific CD4+ and CD8+ T cell response. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD50 per mouse). Studies of the safety and tolerability of the developed vaccine in rodents, rabbits, and primates showed a good safety profile and tolerance in animals; they revealed no contraindications for clinical testing.

A heterologous virus-vectored vaccine for prevention of Middle East respiratory syndrome induces long protective immune response against MERS-CoV

Introduction. Middle East respiratory syndrome (MERS) is acute inflammatory disease of respiratory system with a high mortality, caused Ьу coronavirus MERS-CoV At present moment, we still lack specific therapeutic preparations and vaccines against MERS. Vaccine administration can help to limit the spread of the disease and lower the mortality. Duration of vaccine-induced immune response is one of the key characteristics of a vaccine, which is connected with duration of its protective effectiveness. Unfortunately, the data on duration of vaccine-induced immune response against MERS is scarce. The aim of the study was to determine duration of humoral immune response in mice and primates and duration of protective immune response in mice after immunization with the heterologous virus-vectored vaccine against MERS (BVRS-GamVac-Combi), developed earlier Ьу our research group. Material and methods. To study duration of humoral immune response, we used mice of C57BL/6 strain and common marmosets. Animals were immunized with the vaccine BVRS-GamVac-Combi, based on recomЬinant adenoviral vectors rAd26 and rAd5. Antigen-specific-antibody titers were determined with ELISA, virus-neutralizing antibody titers were measured with virus neutralization assay using MERS-CoV (EMC/2012). To study duration of protective immune response, we used a model of lethal infection on transgenic mice, carrying human DPP4 gene of viral receptor. Results. In present research, we showed that vaccination of animals with BVRS-GamVac-Combi induced robust humoral immune response, which persisted at least 18 months after immunization. In addition, our vaccine protected 100 % of animals from lethal infection for at least 7 months after immunization. Concluslon. Strength of vaccine-induced immune response is generally connected with a protective effectiveness of a vaccine. One of the key problems of vaccine design is to find a way to provide as long and robust immune response as possible. Duration of vaccine-induced immune response is one of the key characteristics of a vaccine, which demands quality control during multiple steps of a vaccine development. Введение. Ближневосточный респираторный синдром (БВРС) - это острое воспалительное заболевание дыхательной системы с высокой летальностью, возбудителем которого является коронавирус БВРС-КоВ. В настоящее время в мире не существует специфических профилактических и терапевтических средств против БВРС. Вакцино-профилактика позволит ограничить распространение данного заболевания и снизить летальность. Одной из ключевых характеристик вакцин является длительность индуцируемого иммунного ответа, от которой зависит продолжительность протективного эффекта вакцины. К сожалению, данных по длительности поствакцинального иммунного ответа для вакцин против БВРС сейчас недостаточно. Цель исследования - определение длительности гуморального иммунного ответа у грызунов и приматов и протективного иммунного ответа после иммунизации комбинированной векторной вакциной против БВРС (БВРС-ГамВак-Комби), разработанной нами ранее. Материал и методы. Длительность гуморального иммунитета исследовали на мышах линии C57BL/6 и обыкновенных игрунках. ЖивРтных иммунизировали вакциной БВРС-ГамВак-Комби на основе рекомбинантных векторов rAd26 и rAd5. Титр антиген-специфических антител определяли методом иммуноферментного анализа (ИФА). Титр вирус-нейтрализующих антител определяли с помощью реакции вирус-нейтрализации против вируса БВРС-КоВ (MERS-CoV EMC/2012). Длительность протективного иммунитета исследовали на модели летальной инфекции у трансгенных мышей, несущих ген человека DPP4, кодирующий рецептор к БВРС-КоВ. Результаты. Исследование длительности поствакцинального гуморального иммунного ответа у грызунов и приматов показало, что вакцинация животных БВРС-ГамВак-Комби индуцирует формирование напряженного гуморального иммунного ответа к гликопротеину S БВРС-КоВ, который сохраняется на протяжении не менее 18 мес. Также было показано, что вакцинация позволяет защитить 100 % животных от летальной инфекции, вызванной БВРС-КоВ (MERS-CoV EMC/2012, 100 ЛД50/мышь), через 7 мес после иммунизации. Заключение. Напряженность поствакцинального гуморального иммунного ответа, как правило, связана с протективностью вакцины. Одной из ключевых задачпри дизайне вакцин является обеспечение наиболее длительного напряженного иммунного ответа. Длительность поствакцинального иммунного ответа - одна из ключевых характеристик вакцин, которая требует контроля на различных этапах их разработки.