mRNA vaccines turned out to be highly effective in combating the COVID-19 pandemic and other viral infections. Despite extensive study of mRNA vaccines in the last five years, the issue of safety of their use is still relevant. The study aimed to assess immunogenicity of two anti-tuberculosis mRNA vaccine doses in female and male rats 2 and 4 weeks after vaccination. Hematological and biochemical parameters of blood were determined within the same timeframe. The dose-dependent nature of mRNA vaccine immunogenicity was confirmed in both females and males. Vaccination led to moderate lymphopenia and neutrophilia in male rats, as well as to apparent dose-dependent and sex-related changes in blood biochemistry parameters at various time points. The findings suggest moderate toxicity of the anti-tuberculosis mRNA vaccine and the importance of assessing its toxic effects at various time points in animals of both sexes.

Background. Studying the characteristics of the course of coronavirus infection caused by SARS-CoV-2 remains relevant due to the high mutagenicity of the virus and the prevalence of the disease in the world. The search for new drugs to eliminate clinical manifestations of COVID-19, as well as against its agent, is essential. During the pandemic caused by SARS-CoV-2, dexamethasone was recognized as the only effective anti-inflammatory drug for the treatment of patients with severe form of the disease, but its use leads to a large number of side effects.The aim. To study the therapeutic effect of the drug Molixan in the treatment of coronavirus infection in model animals – Syrian hamsters.Methods. To assess the effectiveness of the drug Molixan, we carried out a visual assessment of the condition of the lungs using light microscopy and the morphometry of the lung tissue of experimentally infected Syrian hamsters on the day 6 after infection under different Molixan treatment regimens and during dexamethasone therapy. The test drug was administered using three different doses (22.2 mg/kg, 44.4 mg/kg and 88.8 mg/kg, which are equivalent to doses of 3 mg/kg, 6 mg/kg and 12 mg/kg of human body weight) once daily or dividing the dose into two within 12 h interval in case of multiple (5 days) intramuscular administration. Dexamethasone (comparison drug) was administered at a dose of 20 mg/kg once daily for 5 days.Results. The studies showed statistically significant effectiveness of using Molixan at a dose of 44.4 mg/kg, divided into two doses, during 5 days. When compared with untreated hamsters, this treatment regimen reduces the degree of generalization and severity of the inflammatory process in the lungs; and the pathomorphological picture is similar to that observed during treatment with Dexamethasone.Conclusion. The studied drug Molixan is effective as an anti-inflammatory drug in the treatment of the disease caused by SARS-CoV-2.

Введение. Проведен синтез конъюгата, состоящего из метотрексата и бифункционального хелатирующего агента. Подобное соединение отличается свойством таргетности по отношению к очагам аутоиммунных артритов. Цель работы – синтезировать комплекс, содержащий радионуклид лютеций-177, для терапии аутоиммунных артритов. Методика. После проведения синтеза радиохимическую чистоту полученного препарата определяли методом тонкослойной хроматографии. В исследованиях in vivo в качестве тест-системы были задействованы аутбредные крысы, самцы в количестве 12 особей. Перед началом исследования животные были распределены на контрольную группу и исследуемую по биораспределению. Исследование биораспределения радиоконъюгата производилось общепринятым способом прямой радиометрии. Оценка производилась путем прямого сравнения распределения радиофармацевтического препарата в крови и органах животных. С учетом периода полураспада радионуклида 177Lu исследования в контрольных точках при изучении фармакокинетики и биораспределения тестируемых препаратов оценивалось не менее 3 особей животных. Результаты. Радиохимическая чистота синтезированного препарата составила не менее 95%. Исследования биораспределения показали тенденции к накоплению препарата в ткани почек, сердца, легких, в остальных оцениваемых органах и тканях накопление препарата имело умеренный и транзиторный характер. Терапевтический радиофармацевтический препарат продемонстрировал удовлетворительный уровень эффективности в отношении целевой нозологии: отмечалось клинически значимое улучшение и частичное восстановление функций пораженной конечности. Заключение. Результаты исследования могут быть внедрены в практику научной работы по разработке лекарственных средств и средств медицинского применения и являются основанием для проведения расширенного углубленного исследования и оптимизации механизмов таргетного действия исследуемых в данной работе радиофармацевтических лекарственных препаратов. Background. A conjugate consisting of methotrexate and a bifunctional chelating agent was synthesized. This compound is distinguished by its ability to target foci of autoimmune arthritis. Aim. To synthesize a radionuclide 177Lu-based complex for the treatment of autoimmune arthritis. Methods. After synthesis, the radiochemical purity of the complex was determined by thin layer chromatography. In the in vivo study, 12 outbred male rats were used as a test system. Prior to the biodistribution study, the animals were divided into a control group and a study group. The radioconjugate biodistribution was assessed with the generally accepted method of direct radiometry by direct comparison of radiopharmaceutical distribution in blood and organs. Taking into account the 177Lu half-life, at least three animals were assessed at measurement points when studying the radiopharmaceutical pharmacokinetics and biodistribution. Results. The radiochemical purity of the 177Lu-based complex was no less than 95%. Biodistribution studies showed a tendency towards radioactivity accumulation in the kidneys, heart, and lungs. In the remaining assessed organs and tissues, the radioactivity accumulation was moderate and transient. The therapeutic radiopharmaceutical demonstrated a satisfactory effectiveness in relation to the target nosology, autoimmune arthritis, evident as clinically significant improvement and partial restoration of the functions of the affected limb. Conclusion. The results of the study can be implemented in the practice for the development of drugs and medical devices and justify conducting an expanded study and optimizing the mechanisms for targeted action of the radiopharmaceuticals, such as studied in the present work.

mRNK-vakciny pokazali vysokuyu effektivnost' v bor'be s pandemiej COVID-19 i drugimi virusnymi infekciyami. Nesmotrya na intensivnoe izuchenie mRNK-vakcin v poslednie pyat' let, vopros o bezopasnosti ih primeneniya vse eshche ostaetsya aktual'nym. Cel'yu raboty bylo ocenit' immunogennost' protivotuberkuleznoj mRNK vakciny v dvuh dozah u samok i samcov krys cherez 2 i 4 nedeli posle vakcinacii. V eti zhe sroki opredelyali gematologicheskie i biohimicheskie pokazateli krovi. Podtverzhdena dozozavisimost' immunogennosti mRNK vakcin kak u samok, tak i u samcov. Vakcinaciya privela k umerennoj limfocitopenii i nejtrofilii u samcov krys, a takzhe k vyrazhennym dozo- i genderzavisimym izmeneniyam v biohimicheskih parametrah krovi v razlichnyh vremennyh tochkah. Poluchennye rezul'taty svidetel'stvuyut ob umerennoj toksichnosti protivotuberkuleznoj mRNK vakciny i vazhnosti issledovaniya ee toksicheskih dejstvij v razlichnyh vremennyh tochkah u zhivotnyh oboih polov.

Vascular endothelial growth factor receptor-1 (VEGFR-1) plays a critical role in tumor-associated angiogenesis. VEGFR-1 is found on the surface of tumor cells and cells in the tumor microenvironment. Blocking this receptor leads to the suppression of proliferation and increased apoptosis of tumor cells, reduction of tumor vascularization, inhibition of the production of immunosuppressive cytokines by tumor-associated macrophages, and the suppression of tumor invasion and metastasis. The creation of monoclonal antibody drugs that block VEGFR-1 is an urgent task in the development of potential antitumor therapeutic drugs. Target molecules created on the basis of antibodies that bind to VEGFR-1 are a promising basis for the creation of theranostic radiopharmaceuticals for the diagnosis and treatment of malignant neoplasms. To study the therapeutic potential of VEGFR-1 inhibition in breast and colon cancers using antibodies, monoclonal antibodies against recombinant human VEGFR-1 protein are developed. The resulting monoclonal antibodies bind to the VEGFR-1 receptor on the cell surface and effectively inhibit the proliferation of breast and colon cancer cells in vitro, reduce the growth rate of the tumor node in vivo, and prolong the survival of tumor-inoculated mice.

Data are presented on ligands based on bombesin derivatives, which are peptides that specifically bind to gastrin-releasing factor receptors, that are promising for use in nuclear medicine. An analysis of developments related to the creation of radiopharmaceuticals (RPs) based on gastrin-releasing peptide-receptor agonists for radionuclide diagnostics and systemic radiation therapy is carried out. The stages of pharmaceutical development of the first Russian RPs 68 Ga-NOTA-AMBA and 177 Lu-DOTA-AMBA are described, including the synthesis technology using automated modules, as well as drug specifications.

Immunotherapy is a treatment option that is becoming more common for different types of cancer. The idea behind this therapy is to modify the patient's immune system. One type of this therapy involves blocking the binding between PD-1 and PD-L1. By doing so, it enables increased antitumor immune activity. Immune checkpoint inhibitors have shown significant efficacy with high response rates and long-term remission in various types of cancer. Glioblastoma (GBM) is a recurrent tumor characterized by immune evasion mechanisms that resist modern immunotherapy. The literature review analyzed the mechanism of tumor resistance to immune response, specifically PD-1 and PD-L1 expression in GBM. The review presented several clinical studies that showed the results of using immune checkpoint inhibitors in GBM patients. Additionally, the review described other mechanisms of tumor resistance to the activated immune system. All sources were selected using specialized scientific retrieval systems and full-text databases such as Google Scholar, eLIBRARY, PubMed, and Elsevier. Keywords: Glioblastoma, immunotherapy, immune modulation, immune checkpoint inhibitors, PD-1, PD-L1.

Neutrophils are the leading cells of the innate immune system and the main population of leukocytes responsible for the primary reaction of the body to various infectious particles. The latter are destroyed by neutrophils due to the processes of phagocytosis and a cascade of reactions, including a respiratory burst reaction. As a result of the respiratory burst reaction of neutrophils they produce reactive oxygen and halogen species, powerful cytotoxic agents that destroy particles in the phagolysosome. All of these processes require regulation, because overactivation of neutrophils can lead to the damage of the tissues surrounding the focus of inflammation mediated by the reactive forms of oxygen. Proteins of the acute phase of inflammation claim for the role of inflammatory regulators. Previously, we have shown the participation of ceruloplasmin in inhibiting the respiratory burst reaction of neutrophils in blood samples. Fibrinogen, on the contrary, increased the intensity of the respiratory burst reaction. Not for all proteins of the acute phase of inflammation and especially their combinations, the effect on the functions of neutrophils has been studied in detail. In this work the effect of a number of proteins of the acute phase of inflammation (C-reactive protein, serum amyloid A, alpha-1-acid glycoprotein and fibrinogen) on the ability of peripheral blood neutrophils to the respiratory burst reaction was studied for the first time using flow cytometry with the registration of the production of reactive oxygen species in cells of peripheral blood samples. Significant changes in the ability of neutrophils to produce reactive oxygen species were found for a number of combinations of the studied proteins of the acute phase of inflammation. The study of interactions of ceruloplasmin and fibrinogen with peripheral blood neutrophils revealed their membrane localization. It seems promising to identify receptors for proteins of the acute phase of inflammation on the neutrophil membrane.

The pharmaceutical development of innovative radiopharmaceuticals (RPs) based on bispecific high-affinity hypervariable fragments of single-domain monoclonal antibodies (nanoantibodies) to the surface receptors of T-regulatory cells (GITR and CTLA-4) is described: 68 Ga-DFO-anti-CTLA4-GITR and 177 Lu-DOTA-anti-CTLA4-GITR. The specified RPs are intended for diagnostics using the immuno-PET method ( 68 Ga-DFO-anti-CTLA4-GITR) and systemic radiation therapy ( 177 Lu-DOTA-anti-CTLA4-GITR) of the generalized forms of socially significant cancer. As part of pharmaceutical development, technologies are created for introducing chelating groups into the bispecific nanoantibody molecule, as well as methods for obtaining the main active substance and the finished dosage form of the radioactive drug with selection of the optimal composition of excipients to ensure the stability of the radionuclide complex and the precursor molecule.

Nuclear medicine was developed at the beginning of the 20th century, when John Lawrence first tested therapy with artificially produced radioisotopes in humans. The study of nuclear-physics methods has made it possible to develop breakthrough technologies in the diagnosis and treatment of various diseases, thereby increasing the duration and improving the quality of life of patients. Today, nuclear medicine is a large-scale area in clinical practice that requires comprehensive regulatory and methodological regulation. Information is presented both on the issues of legitimizing this industry as a whole, and on the development of regulatory and methodological documentation on the quality and safety of the use of nuclear-physics technologies, and the development of radiopharmaceutical drugs in terms of preclinical and clinical studies.

Введение. Своевременная диагностика лечение и профилактика неалкогольной жировой болезни печени остаются одними из наиболее актуальных медицинских и социальных проблем. Ключевую роль в изучении этиологии и механизмов патогенеза играет поиск адекватной экспериментальной модели неалкогольной жировой болезни печени. Принимая во внимание патогенетические особенности развития данной патологии, интерес представляет разработка модели с помощью воздействия на подопытных животных гиперкалорийной гепатогенной диетой, содержащей повышенное количество углеводов. Эта модель применена в настоящем исследовании. Цель исследования - анализ биохимического профиля и наиболее значимых маркеров антиоксидантной системы у крыс на фруктозоиндуцированной модели неалкогольной жировой болезни печени Методика. Отработаны модели неалкогольной жировой болезни печени различной степени тяжести у крыс: легкая степень тяжести - неалкогольный стеатоз печени и средняя степень - неалкогольный стеатогепатит. Исследование проведено на 100 самцах крыс Wistar. Моделирование неалкогольного стеатоза осуществлялось путем замены питьевой воды на 10-процентный раствор фруктозы. Крысы, у которых моделировали развитие стеатогепатита получали сухой гранурированный корм, содержащий по массе 60% фруктозы. Определяли следующие биохимические показатели: уровень глюкозы, общее содержание белков в плазме крови, концентрацию общего билирубина и его прямой фракции, активность аланинаминотрансферазы, аспартатаминотрансферазы, лактатдегидрогеназы и щелочной фосфатазы, уровень гомоцистеина, содержание общего холестерина, триацилглицеридов. каталазы, супероксиддисмутазы и малонового диальдегида. Результаты. Воспроизведенные нами модели характеризовались развитием билирубинемии, холестеринемии, активацией перекисного окисления липидов и супрессией антиоксидантных механизмов, цитолитическим и холестатическим синдромами. Степень нарушения обмена веществ крыс зависела от степени тяжести моделируемого заболевания. Заключение. Показана целесообразность определения биохимических маркеров: активность аланинаминотрансферазы, аспартатаминотрансферазы, уровень общего билирубина, триглицеридов, малонового диальдегида, супероксиддисмутазы с целью определения степени тяжести неалкогольной жировой болезни печени и своевременной коррекции метаболических нарушений. Timely diagnosis, treatment, and prophylaxis of non-alcoholic fatty liver disease remain one of the most important medical and social problems in spite of long-standing, extensive studies of the pathogenesis of this disease. A search for an adequate experimental model for non-alcoholic fatty liver disease plays a key role in the studies of its etiology and mechanisms. Taking into consideration all pathogenetic peculiarities of this pathology, of the utmost interest is developing an animal model using a hypercaloric, hepatogenic diet rich in carbohydrates. This particular approach was used in the present study. The aim of the study was to assess changes in the biochemical profile, as well as in the most significant markers of the antioxidant system in a rat model of fructose-induced, non-alcoholic fatty liver disease. Methods. Non-alcoholic fatty liver disease models of varying severity were used: mild non-alcoholic steatosis and moderate non-alcoholic steatohepatitis. The study was conducted on 100 male Wistar rats. Non-alcoholic steatosis was modeled by replacing the drinking water with a 10% solution of fructose. Development of steatohepatitis was simulated by a dry granular diet containing 60% fructose by weight. The following biochemical parameters were measured: plasma concentrations of plasma glucose, total protein, total bilirubin and its direct fraction, enzyme activities of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase, and plasma concentrations of homocysteine, total cholesterol, triacylglycerides, catalase, superoxide dismutase, and malonic dialdehyde. Results. Both models were characterized with bilirubinemia, cholesterolemia, lipid peroxidation activation and antioxidation mechanism suppression, cytolytic and cholestatic syndromes. The extent of the metabolic disorders depended on the severity of the modeled ailment. Conclusion. The study demonstrated the expediency of determining biochemical markers, including levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, triglycerides, malondialdehyde, and superoxide dismutase, to determine the severity of non-alcoholic fatty liver disease and the timely correction of the related metabolic disorders.

It is important to understand the features of the interaction of drug components with body receptors and obtain data on its distribution in various administration routes in recommended doses in order for its usage in clinical practice to be safe and effective.PURPOSE:To investigate in vitro the interactions of a drug consisting of water-soluble polypeptide fractions produced on animal retina with a wide range of receptor targets, and to assess its biodistribution in the organs of laboratory animals.MATERIAL AND METHODS:The biodistribution of the radioactively marked drug in different organs and tissues of laboratory mice in various routes of administration was studied at the National Research Centre «Kurchatov Institute». Evaluation of the ligand-receptor interaction of the drug was carried out in the laboratory at Eurofins Pharma Discovery Services by the method of competitive radioligand binding.RESULTS:A significant effect of the interaction of the polypeptide drug was revealed with different subtypes of glutamate receptors: AMPA, NMDA, and mGluR1. As a result of an in vivo test, we have obtained biodistribution data of the drug for intravenous, intramuscular and parabulbar administration, and the dynamics of drug accumulation in the tissues of the brain and eyes.CONCLUSION:According to the study results, the peptide drug binds to receptors associated with the loss of retinal ganglion cells. Interaction with these receptors potentially provides the test subject with neuroprotective effect. The content dynamics of the studied drug in the blood of animals depends on the route of administration and the amount of drug administered. At the time point of 0.5 hours for intravenous and intramuscular administration in the dose of 1.7 mg/kg, the studied drug has sufficiently high bioavailability in the tissues of the brain and eye. The data suggest that the main route of excretion of the studied drug is through kidneys.

Detailed clinical assessment of the central nervous system involvement in SARS-CoV-2 infection is relevant due to the low specificity of neurological manifestations, the complexity of evaluation of patient complaints, reduced awareness of the existing spectrum of neurological manifestations of COVID-19, as well as low yield of the neurological imaging. The aim . To reveal the patterns of central nervous system involvement in COVID-19 and its pathogenesis based on clinical data. Among more than 200 primary literature sources from various databases (Scopus, Web of Science, RSCI, etc.), 80 sources were selected for evaluation, of them 72 were published in the recent years (2016-2020). The criteria for exclusion of sources were low relevance and outdated information. The clinical manifestations of central nervous system involvement in COVID-19 include smell (5-98% of cases) and taste disorders (6-89%), dysphonia (28%), dysphagia (19%), consciousness disorders (3-53%), headache (0-70%), dizziness (0-20%), and, in less than 3% of cases, visual impairment, hearing impairment, ataxia, seizures, stroke. Analysis of the literature data revealed the following significant mechanisms of the effects of highly contagious coronaviruses (including SARS-CoV-2) on the central nervous system: neurodegeneration (including cytokine- induced); cerebral thrombosis and thromboembolism; damage to the neurovascular unit; immune-mediated damage of nervous tissue, resulting in infection and allergy-induced demyelination. The neurological signs and symptoms seen in COVID-19 such as headache, dizziness, impaired smell and taste, altered level of consciousness, bulbar disorders (dysphagia, dysphonia) have been examined. Accordingly, we discussed the possible routes of SARS-CoV-2 entry into the central nervous system and the mechanisms of nervous tissue damage. Based on the literature analysis, a high frequency and variability of central nervous system manifestations of COVID-19 were revealed, and an important role of vascular brain damage and neurodegeneration in the pathogenesis of COVID-19 was highlighted.

The genotoxic and antigenotoxic potential of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, was investigated as a radioprotector/radiomitigator for civil applications and as a medical countermeasure for radiation emergencies. Using the alkaline comet assay and methyl methanesulfonate (MMS, 40 mg/kg) as the DNA-damaging agent, these effects of BP-C2 on liver, bone marrow cells and blood leukocytes in rats were studied. The DNA damage was estimated by the DNA content in the comet tail (TDNA, %) 1, 6 and 18 h post exposure to MMS. BP-C2 at doses of 20, 200 and 2000 mg/kg did not exert genotoxic activity in the tested tissues in rats. BP-C2 administered at doses of 20, 100 and 200 mg/kg 1 h before MMS significantly (p < 0.01) mitigated MMS-induced DNA damage, showing a strong genoprotective effect in the liver. In blood leukocytes and bone marrow samples of animals treated with BP-C2, the TDNA % was slightly higher than in the negative control (vehicle) but significantly lower than in the positive control (MMS). Thus, BP-C2 exerted a genoprotective effect against MMSinduced DNA damage to a greater extent towards liver cells, requiring further evaluation of this substance as a genoprotective agent.

Введение. Изучение роли олигомерных форм уромодулина в развитии уролитиаза является важной фундаментальной и прикладной задачей. Несмотря на разнообразие моделей уролитиаза на лабораторных животных в настоящее время отсутствует информация относительно динамики концентрации и фракционного состава олигомерных форм уромодулина в моче животных на различных этапах развития патологического процесса. Цель - исследование динамики содержания олигомерных форм уромодулина в моче животных на фоне развития гипероксалатного уролитиаза индуцированного экзогенным введением 1% раствора этиленгликоля в качестве безальтернативного источника питья. Методика. Проводили общеклинический и биохимический анализ образцов крови и мочи на различных этапах развития патологического процесса. До начала моделирования патологии и на фоне экзогенного введения этиленгликоля был исследован осадок мочи. Оценка содержания олигомерных форм уромодулина в моче животных проводилась методом анализа треков наночастиц и динамического рассеяния света. Результаты. Показано, что на фоне развития патологии наблюдается уменьшение концентрации олигомерных форм уромодулина в моче, на начальных этапах развития патологии за счёт увеличения фракции крупных частиц (более 200 нм, олигомерная форма 28 МДа). При дальнейшем развитии патологического процесса на завершающем этапе наблюдается радикальное уменьшение концентрации частиц в моче (более чем в 2 раза). Заключение. Полученные данные показали относительно низкую корреляцию между длительностью моделирования патологии и тяжестью проявления уролитиаза (r-Пирсона = 0,49, p-value = 0,0003). Концентрация олигомеров уромодулина в моче животных уменьшается на фоне увеличения количества кристаллов в осадке мочи, что вероятно связанно с включением уромодулина в структуру кристаллов осадка. Studying uromodulin oligomeric forms in urolithiasis development is important fundamental and applied problem. Despite the variety of in vivo models of urolithiasis, there is currently no information about concentration dynamics and fractional composition of uromodulin oligomeric forms in urine for animals at various stages of pathological process developmen. The purpose We investigate dynamics uromodulin oligomeric forms in urine of animals against the background of development hyperoxalate urolithiasis induced by exogenous administration of 1% ethylene glycol solution as a non-alternative source of drinking. Methods. For urine samples at various stages of pathogenesis, general clinical and biochemical analysis were carried out, for urine samples before the start of pathology modeling and against the background of exogenous administration of ethylene glycol, urine sediment was examined. The study of urine sediment and content uromodulin oligomeric forms was carried out on 0th, 7th, 14th, 21st and 28th days of pathology modeling. Evaluation of the content of uromodulin oligomeric forms in urine of animals was carried out by nanoparticles track analysing and dynamic light scattering. Results. It is shown that against the background of the pathology development there is a decrease in the concentration of oligomeric forms of uromodulin in the urine, at the initial stages of pathology development due to an increase in the fraction of large particles (over 200 nm, oligomeric form 28 МDa). With further development of the pathological process at the final stage, there is a radical decrease in the concentration of particles in the urine (more than 2-fold). Conclusion. The obtained data showed a relatively low correlation between the duration of pathology modeling and the severity of urolithiasis manifestation (Pearson's r = 0.49, p-value = 0.0003). Concentration of uromodulin oligomers in animals urine decreases with an increase in the amount of crystals in urine sediment, which is probably associated with inclusion of uromodulin in structure of sediment crystals.

Detailed clinical assessment of the central nervous system involvement in SARS-CoV-2 infection is relevant due to the low specificity of neurological manifestations, the complexity of evaluation of patient complaints, reduced awareness of the existing spectrum of neurological manifestations of COVID-19, as well as low yield of the neurological imaging.The aim. To reveal the patterns of central nervous system involvement in COVID-19 and its pathogenesis based on clinical data.Among more than 200 primary literature sources from various databases (Scopus, Web of Science, RSCI, etc.), 80 sources were selected for evaluation, of them 72 were published in the recent years (2016-2020). The criteria for exclusion of sources were low relevance and outdated information.The clinical manifestations of central nervous system involvement in COVID-19 include smell (5-98% of cases) and taste disorders (6-89%), dysphonia (28%), dysphagia (19%), consciousness disorders (3-53%), headache (0-70%), dizziness (0-20%), and, in less than 3% of cases, visual impairment, hearing impairment, ataxia, seizures, stroke. Analysis of the literature data revealed the following significant mechanisms of the effects of highly contagious coronaviruses (including SARS-CoV-2) on the central nervous system: neurodegeneration (including cytokine- induced); cerebral thrombosis and thromboembolism; damage to the neurovascular unit; immune-mediated damage of nervous tissue, resulting in infection and allergy-induced demyelination.The neurological signs and symptoms seen in COVID-19 such as headache, dizziness, impaired smell and taste, altered level of consciousness, bulbar disorders (dysphagia, dysphonia) have been examined. Accordingly, we discussed the possible routes of SARS-CoV-2 entry into the central nervous system and the mechanisms of nervous tissue damage.Based on the literature analysis, a high frequency and variability of central nervous system manifestations of COVID-19 were revealed, and an important role of vascular brain damage and neurodegeneration in the pathogenesis of COVID-19 was highlighted.

1 St. Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation, 2, Litovskaya ul., St. Petersburg, 194100, Russian Federation 2 St. Petersburg State University, 7–9, Universitetskaya nab., St. Petersburg, 199034, Russian Federation 3 St. Petersburg Research Institute of Phthisiopulmonology, Health Ministry of Russia, 2–4, Ligovskiy pr., St. Petersburg, 191036, Russian Federation 4 Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44, Thoreza pr., St. Petersburg, 194223, Russian Federation 5 Petersburg Nuclear Physics Institute named after B. P. Konstantinov of National Research Centre “Kurchatov Institute”, 1, mkr. Orlova roshcha, Leningradskaya oblast, Gatchina, 188300, Russian Federation 6 Peter the Great St. Petersburg Polytechnic University, 29, Polytechnicheskaya ul., St. Petersburg, 195251, Russian Federation