Search

The article presents a case of ischemic stroke after SARS-CoV-2 infection in a patient with dyscirculatory encephalopathy and schizophrenia. Patient 44 years old, was hospitalized due to a confirmed diagnosis of a new coronavirus infection (COVID-19) and diagnosed bilateral pneumonia with a damage to 65% of the lung parenchyma. The patient has a history of dyscirculatory encephalopathy and paranoid schizophrenia, a continuous type of course. A fatal outcome occurs on the 2 nd day of inpatient treatment. A brain autopsy revealed pericellular and perivascular edema, looseness of neuroglia with necrobiotic changes in the brain substance. Neuronal damage, small-focal gliosis, basophilic balls, destructive-productive vasculitis, ischemic small-focus necrosis were revealed. In the lungs, areas of atelectasis, disatelectasis, hyaline membranes, and edematous fluid were found. Epithelium of the convoluted tubules showed dystrophic and necrotic changes. The cause of death of the patient was a new coronavirus infection COVID-19, which caused bilateral viral pneumonia, complicated by the development of acute respiratory failure and COVID-associated ischemic cerebral infarction complicated by neuromorphological changes in the brain.

The review presents the basic information available in the literature on the structural proteins of SARS-CoV-2 (S;N;E;M). Issues affecting the importance of these proteins in the pathogenesis, adaptation and life cycle of the virus are discussed. Structural multifunctional proteins are biomarkers of increased contagiousness and pathogenicity of SARS-CoV-2, forming its pathogenetic and adaptive potential. The multifunctionality of the structural proteins of the new coronavirus allows it to respond quickly to fluctuations in the conditions of existence through the use of alternative approaches to implement the mechanisms underlying its pathogenetic potential. Currently, the structure, properties, functions and role of structural proteins of SARS-CoV-2 are being actively studied, which is an actual vector of research that allows us to decipher the mechanisms underlying its high contagiousness, pathogenicity, adaptation, and in the future to evaluate possible ways of forming its new variants and develop a strategy and tactics of emergency response when it appears new strains.The prospects of further study of the structure and properties of structural proteins for solving the priority tasks of the present time on the creation of modern domestic vaccines and effective methods of diagnosis, treatment and prevention of a new coronavirus are noted.The authors analyzed scientific publications from various databases of electronic libraries, such as PubMed, e-library, CyberLeninka, etc.

Aim. The study is aimed at describing pancreatic islets as one of the SARS-CoV-2 targets.Materials and methods. The object of the study was the pancreas. The study involved histological staining.Results and discussion. The autopsy study revealed the signs typical of bilateral viral interstitial pneumonia. Histological examination revealed alveoli with disatelectasis, intra-alveolar edema, hyaline membranes in a part of alveoli. The pancreas histological examination showed hemorrhages, necrotic areas of the islets and detected the following DIC signs: small hyaline thrombi in the heart cavities and large vessels, petechial hemorrhages in the internal organs and adrenal glands, foci of adrenal cortex necrosis with perifocal infiltration (Waterhouse—Friderichsen syndrome); as well as signs of necronephrosis with fibrinoid areas of necrosis in the glomerular capillary network and perivascular lymphoid infiltrates.Conclusion. SARS-CoV-2 was revealed to target human pancreatic islets, where areas of necrosis developed.

Aim: to build a predictive model for severe COVID-19 prediction in young adults using deep learning methods. Materials and methods: data from 906 medical records of patients aged 18 to 44 years with laboratory-confirmed SARS-CoV-2 infection during 2020–2021 period was analyzed. Evaluation of laboratory and instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p≤0,05. The neural network was trained using the Pytorch framework. Results: in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum iron, transferrin, and absolute peripheral blood eosinophil and lymphocyte counts were significantly higher than in patients with severe СOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood pressure in the group of patients with mild and moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and their threshold values. A model intended to predict COVID-19 severity in young adults was built. Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based on artificial intelligence method with high accuracy predicts the likelihood of severe SARS-CoV-2 course development in young adults.

Russian and foreign epidemiological data suggest that males may have an increased risk of morbidity and mortality associated with COVID‑19. It is known that due to the high expression of ACE2 in spermatogonia, Leydig and Sertoli cells, the testicle, as an organ producing male germ cells, is a potential target for the COVID‑19 virus, which directly affects the reproductive health of men. To date, several factors of the influence of the SARS-CoV‑2 virus on the male reproductive system are known. To begin with, when infected, the virus has a direct damaging effect on the testicle itself with the provocation of orchitis. In addition to the previous statement, high body temperature during inflammation contributes to an increase in testicular temperature, which can lead to a deterioration in the quality of sperm. Furthermore, a pronounced inflammatory reaction promotes the circulation of a large number of cytokines and damage to the hemato-testicular barrier. Also, the increased activity of immunocytes leads to an imbalance of the antioxidant system of men, an increase in the level of reactive oxygen species and the formation of oxidative stress. In a Nutshell, Leydig cell dystrophy provokes the development of secondary hypogonadism. Thus, COVID‑19, like a “multifaceted Janus”, has a polysymptomatic manifestation, but at the same time has a multifactorial effect on the reproductive function of a man. All these factors of the impact of the SARS-CoV‑2 virus on the testicle must be considered when rehabilitating the patient. It should be kept in mind that the deterioration of sperm quality is observed both during the acute period of coronavirus infection and during recovery period. Therefore, laboratory evaluation of the ejaculate in dynamics and its correction is necessary for males, especially those who plan to realize their reproductive potential.Conclusion. COVID‑19 generally has a negative impact on spermatogenesis and male fertility. To date, the timing and degree of restoration of a man’s reproductive function after a coronavirus infection remains completely unknown. Therefore, both in the early and late rehabilitation period, men of reproductive age need the supervision of an andrologist.

In COVID-19, eye damage may develop at any stage of the disease. Viral ribonucleic acid has been found in ocular tissues, but the role of the eye as a route of infection is yet to be substantiated. Ophthalmic manifestations may be a typical feature of COVID-19 infection or they may develop several weeks after recovery. Ophthalmologists should be aware of possible relationships of an ophthalmic pathology with SARS-CoV-2 in order to obtain targeted case history, detect the specific signs, prescribe the necessary tests and thereby reduce the spread of the infection. These relationships are also important for early diagnosis and treatment of complications that threaten the patients’ life and vision. The first part of the review focuses on the possible involvement of the eye in SARS-CoV-2 infection and the spread of infection. Clinical manifestations of the anterior segment damage are considered.

Currently, the disease caused by the new coronavirus (COVID-19) and the possibility of co-infection with SARS-CoV-2 and other pathogens in the current epidemic situation continues to be of particular interest. The review, based on the analysis of literature and own materials, outlines the features of the relationship between SARS-CoV-2 and pathogens of acute respiratory viral infections (ARVI). Particular attention is paid to the combined course of COVID-19 and influenza, a comparative characteristic of the severity of the clinical picture. An assessment of the epidemic situation against the backdrop of the COVID-19 pandemic in foreign countries and the Russian Federation (RF) revealed the presence of the phenomenon of SARS-CoV-2 interference with other viral respiratory agents, based on the facts of a sharp suppression of the circulation of influenza viruses, respiratory syncytial virus (RSV) and other ARVI pathogens during the period of active spread of pandemic coronavirus. The main epidemiological indicators of the course of coronavirus infection were compared and the contribution of various pathogens to the etiology of acute respiratory viral infections during the development of the second wave of COVID-19 in the RF was assessed. It was noted that the decrease in the number of new cases by 11.4 and deaths by 2.1 times due to COVID-19 at 6 and 13 weeks in 2022 occurred with unchanged laboratory detection of the influenza virus (0.8%) and an increase in the frequency detection of pathogens of other SARS. The results of observations showed that against the background of a decrease in the incidence of COVID-19, there was no increase in the proportion of diagnosed cases of infections caused by other pathogens, especially influenza. The results obtained confirm the need to ensure effective epidemiological surveillance and additional application of pathogen identification methods for monitoring various ARVI, which can significantly affect the approach to differential diagnosis, patient management tactics and the decision on appropriate preventive measures.

The development of COVID-globulin, a COVID-19-specific human immunoglobulin preparation, involved choosing a method to quantify antibodies to SARS-CoV-2. Antibody titre determination by virus neutralisation (VN) is labour-intensive and unsuitable for large-scale application. To enable routine testing, it was necessary to develop a less demanding method; the enzyme-linked immunosorbent assay (ELISA) was the most appropriate of solutions. The lack of international and industry reference standards (RS) prompted the preparation and certification of an RS for COVID-globulin potency control.The aim of the study was to examine the possibility of substituting ELISA for VN and to develop an RS for SARS-CoV-2 antibody quantification in immunoglobulin preparations.Materials and methods: the authors used commercial ELISA kits by several manufacturers, COVID-globulin by Microgen (48 batches), and human plasma samples from multiple sources (1499 samples). The tests were performed by VN, ELISA, and chemiluminescent microparticle immunoassay.Results: the authors validated an ELISA method for SARS-CoV-2 antibody quantification with the selected reagent kits by the National Medical Research Center for Hematology (NMRC for Hematology) and Euroimmun AG. The authors demonstrated the possibility of using ELISA instead of VN (with a correlation coefficient of more than 0.9). They developed and characterised an in-house RS for SARS-CoV-2 antibody content in human immunoglobulin preparations. The RS was certified in newly introduced anti-COVID units (ACU) and in international binding antibody units (BAU) using the World Health Organisation (WHO) international reference panel (NIBSC code: 20/268). The RS's potency was measured in terms of its neutralising activity in ACU (320 ACU/mL) and BAU (2234.8 BAU/mL). The authors established the relationship between ACU and BAU units. For the selected ELISA reagent kits, the conversion factors were 6.4 (NMRC for Hematology) and 7.0 (Euroimmun AG).Conclusions: the ELISA method for SARS-CoV-2 antibody quantification and the RS for SARS-CoV-2 antibody content can be applied to determine the potency of human anti-COVID-19 immunoglobulins.

The COVID-19 pandemic has stimulated interest in the development of biotechnology, as well as in the search for new solutions in the diagnostics of immune processes. The response of immunoglobulins A, M and G had a significant role in the assessment of virus-specific immune responses. Later, it was understood that for a comprehensive assessment of adaptive immunity processes, it is reasonable to study its cellular component. One of the most affordable methods for assessing T cell immunity, which has proven itself in the diagnosis of other infectious diseases, such as latent tuberculosis infection, is IGRA ELISPOT.The aim of the study. To determine SARS-СoV-2 specific immune response of T lymphocytes in vitro in the peripheral blood of volunteers from various groups using IGRA ELISPOT method. We evaluated the applicability of the method to assess T cell immune response to infection and vaccination. In addition, we determined the duration of the maintenance period of the SARS-CoV-2 specific T cells immune response induced by vaccination.Materials and methods. The study was carried out on venous blood samples of volunteers from three groups: 1) hospital patients with COVID-19; 2) COVID-19 convalescents; 3) vaccinated against COVID-19. The T cell immune response was assessed using the TigraTest® SARS-CoV-2 test system, which determines in vitro the number of T cells secreting interferon-gamma in response to stimulation with SARS-СoV-2 peptides in two antigens panels: 1) peptides of the spike protein (S); 2) peptides of N, M, Orf3a and Orf7a proteins.Conclusion. The IGRA ELISPOT assay is a specific and sensitive tool in the assessment of T cell immunity to the SARS-CoV-2 virus. The method makes it possible to assess SARS-CoV-2 specific T cell responses induced both by natural encounter with the pathogen and by vaccination. It is advisable to use the method in routine practice for comprehensive assessment of immunity to SARS-CoV-2.

Introduction. Convalescent COVID-19 patients have various signs of central nervous system damage, including those directly associated with SARS-CoV-2. Hence, studies of SARS-COV-2 related morphological changes in neocortex are particularly relevant for understanding the mechanisms of their formation and development of approaches to preclinical evaluation of the effectiveness of antiviral drugs. The purpose of the research is a longitudinal study of the ultrastructural alterations in Syrian hamsters neocortex after experimental SARS-CoV-2 infection. Materials and methods. Male Syrian hamsters weighing 80100 g, aged 4 to 6 weeks, were infected with 26 l SARS-CoV-2 intranasally with 4104 TCD50/ml of viral particles. The animals were euthanized on days 3, 7 or 28 post-infection, the brain was extracted with the cortex excision. The material analysis was performed using transmission electron microscopy. Results and discussion. On day 3 post-infection, the number of moderately hyperchromic neurons in neocortex increased, while by the day 7 the number of apoptotic cells significantly increased. Simultaneously, an increased signs of neuronophagy and representation of atypical glia were observed. Increased number of altered oligodendrocytes was observed on day 28 post-infection. Viral invasion was accompanied by changes in neocortical cells since day 3 post-infection, such as transformation of their nucleus, the rough endoplasmic reticulum and the Golgi vesicles as well as microvascular spasm with perivascular edema. Conclusion. As a result of electron microscopic study, the ultrastructural alterations in neocortex were described in an experimental model of SARS-CoV-2 infection. The findings can be used to identify the mechanisms of infection pathogenesis and to search for the new directions in development of medicines.

Confirming detected SARS-CoV-2-specific antibodies is necessary to reveal immune response in COVID-19 convalescent subjects as well as to conduct population studies by screening for specific antibodies to assess rate of COVID-19 prevalence. With this purpose St. Petersburg Pasteur Institute was the first in Russia to develop the ELISA kit for the quantitative determination of human IgG to the SARS-CoV-2 nucleocapsid (N-CoV-2-IgG PS). Arbitrary units (AU/ml) were used to assess the level of antibodies. The data shown in AU/ml were recalculated later to the international units (BAU/ml) in accordance with established the First WHO International Standard for anti-SARS-CoV-2 human Immunoglobulin. Comparing the data of the N-CoV-2-IgG PS calibration curve with those of the First WHO International Standard for anti-SARS-CoV-2 human Immunoglobulin revealed a complete inter-assay association (r = 0.999, R2 = 0.997) allowing to find that 1BAU/ml = 5.97 AU/ml. The aim of the study was to characterize the SARS-CoV-2 protein N Human IgG Quantitative ELISA Kit (N-CoV-2-IgG PS), compare quantitative and qualitative data of ELISA kits, assess a correlation between the binding antibodies to SARS-CoV-2 N proteins and the neutralizing antibodies against SARS-CoV-2. The data of correlation analysis of the 83 COVID-19 convalescent blood plasma samples a significant relationship between the antibodies quantitative values and titers SARS-CoV-2-specific antibody (r = 0.8436, R2 = 0.7802) as well as a moderate relationship between antibody concentration and positivity index (r = 0.6648, R2 = 0.3307), assessed by Chaddock scale. Comparing concentration of N-protein binding antibodies with neutralizing antibody titers level uncovered data consistency obtained by quantitative and virus microneutralization assays (r = 0.7310, R2 = 0.6527) used in parallel to analyze 80 blood plasma samples obtained from COVID-19 patients and convalescents. AUC under the ROC curve comprised 0.701 (P 0.0001) evidencing about a satisfactory informative value for N-CoV-2-IgG PS compared with microneutralization assay. In addition, the efficacy of the N-CoV-2-IgG PS was 95%, while the positive and negative prognostic value was 97% and 87%, respectively. The data obtained confirmed a correlation between N-protein binding antibody level and neutralizing antibody titer. Checking inter-assay agreement evidenced about acceptance for informativeness and efficacy of using N-CoV-2-IgG PS, thereby confirming an opportunity to apply the Kit to screen for SARS-CoV-2 N protein-specific IgG antibody level and assess seroprevalence in diverse population cohorts.

To date, there is no consensus explaining the relationship between varying concentrations of IFNγ and the severity of infection caused by SARS-CoV-2. The aim of this article was to analyze and formulate conclusions from the selected studies and publications, which, in sum, provide a potentially reasonable view on the role of IFNγ in COVID-19 pathogenesis. This article highlights current data on the immunological role of IFNγ which affects differentiation of naive T helper cells, acting as a polarizing factor. It activates the major histocompatibility complex (MHC) class I and II, by increasing the expression of MHC I/II subunits, inhibiting replication of the viral particles by initiating activation of interferon-stimulated genes followed by subsequent synthesis of antiviral proteins. Moreover, IFNγ activates the production of cytokines by T cells, enhancing cytotoxic activity of the T killers. IFNγ exerts immunostimulatory and immunomodulatory effects via STAT1, SOCS1 and PIAS genes, thus regulating activation of the JAK-STAT signaling pathway. A number of studies were considered where the patterns of changes in serum IFNγ concentration were examined in viral infections and SARS-CoV-2. We performed a systemic analysis of the results of studies that showed a relationship between high concentrations of IFNγ and COVID-19 severity. In a number of studies, the significantly high levels of IFNγ in COVID-19 patients were often associated with a poor outcome of the disease. The median values of the IFNγ concentration in severe COVID-19 were found to be significantly higher compared to the results obtained in the cases of moderate severity. It shows an increase, in parallel with viral load in the nasopharyngeal samples upon worsening of the clinical condition. Based on the data on the decreased IFNγ concentrations in convalescent patients, the mechanism of antagonism between IFNγ and IL-4 is considered, where the decreases serum concentrations of IFNγ along with increasing level of IL-4 may be an indirect proof of normal adaptive immune response with subsequent development of antibodies to SARS-CoV-2 and gradual elimination of the virus from the body. Moreover, the evidence is discussed that the patients harboring some parasitic infections (Toxoplasma gondii, Cryptosporidium, Blastocystis hominis, Giardia duodenalis, Entamoeba histolytica) with persistently elevated level of IFNγ are at reduced risk for severe course of COVID-19.

ПРЕДПОСЫЛКИ: Проблема эффективности вакцинации в отношении вирусов, претерпевающих постоянные антигенные изменения в процессе эволюции, в настоящее время решается за счет обновления состава вакцин для обеспечения соответствия циркулирующим штаммам. В случае внезапного появления в популяции вируса, значительно отличающегося от циркулирующего (антигенный шифт или дрейф), или нового вируса, каким стал SARS-CoV-2, этот подход не работает. В связи с этим существует необходимость создания универсальной вакцины, индуцирующей Т-клеточный иммунный ответ к консервативным антигенным детерминантам вируса. ЦЕЛЬ ИССЛЕДОВАНИЯ: Получение вакцинного кандидата на основе аттенуированного гриппозного вектора для иммунизации с целью индукции защиты от гетерологичного вируса гриппа и коронавируса. МЕТОДЫ: На основе вируса гриппа A/Puerto Rico/8/1934 (H1N1) (PR/8/34) был сконструирован рекомбинантный вектор FluCoV-N, содержащий аттенуирующие мутации в генах ns1 и nep и экспрессирующий N-концевую последовательность белка N (N 1-209 ) вируса SARS-CoV-2. Для моделирования защиты хорьков от гриппа через 25 дней после однократной вакцинации вектором в дозе 9.4 log 10 ЭИД 50 их заражали гетерологичным штаммом вируса гриппа A/Austria/1516645/2022 (H3N2). Для проверки защиты хомяков от коронавируса проводили их однократную иммунизацию вектором в дозе 8.2 log 10 ЭИД 50 , а через 21 день их инфицировали SARS-CoV-2. РЕЗУЛЬТАТЫ: Полученный вектор характеризовался температурочувствительностью (ts), способностью к стимуляции системы интерферонов I типа (IFN I) и безвредностью для животных при интраназальном применении в высокой дозе. Однократная интраназальная иммунизация хорьков FluCoV-N приводила к ускоренному разрешению инфекции, вызванной гетерологичным вирусом гриппа H3N2. Аналогичная иммунизация хомяков обеспечивала снижение титров вируса SARS-CoV-2 в легких в 10000 раз на второй день после инфекции и уменьшала патологию в легких животных. ЗАКЛЮЧЕНИЕ: Однократная интраназальная иммунизация хорьков или хомяков гриппозным вектором FluCoV-N защищала животных, ослабляя развитие заболевания, вызванного гетерологичным вирусом гриппа или SARS-CoV-2 соответственно.

Introduction and purpose: The COVID-19 pandemic has significantly affected the health, life and quality of life of many people around the world. It caused huge changes in the daily functioning of entire societies. Pregnant women are a unique group of people who are particularly at risk. They are accompanied by fear for their health, but also fear of the impact of the disease on their offspring. The pandemic has also caused new challenges for mothers-to-be that have not occurred so far. In this paper, we would like to present the current state of knowledge on the impact of SARS-CoV-2 infection on the risk of developing pre-eclampsia. State of knowledge: We analyzed studies showing the impact of COVID-19 infection on the health of pregnant women, especially on the risk of developing pre-eclampsia. Data from many studies are contradictory. Some studies do not indicate a significant impact of coronavirus infection on the development of pre-eclampsia. Some of them confirm a higher incidence of pre-eclampsia in pregnant women with confirmed COVID-19 infection. Conclusions: Despite the experience gained, there are still many unknowns. Thanks to research, we have more and more knowledge about the course of COVID-19 in pregnant women and its impact on their lives. Many observations are still needed to formulate clear conclusions about the impact of COVID-19 on the risk of developing pre-eclampsia. It is also necessary to continue to educate women, encourage compliance with the recommendations of doctors and the World Health Organization to prevent the spread of coronavirus.

Introduction: SARS-CoV-2 infection causes immune disorders that create conditions for the reactivation of human herpesviruses (HHVs). However, the estimates of the HHVs effect on the course and outcome of COVID-19 are ambiguous. Аim - to study the possible relationship between the HHV reactivation and the adverse outcome of COVID-19., Materials and Methods: Postmortem samples from the brain, liver, spleen, lymph nodes and lungs were obtained from 59 patients treated at the Moscow Infectious Diseases Hospital No.1 in 2021-2023. The group 1 comprised 39 patients with fatal COVID-19; group 2 (comparison group) included 20 patients not infected with SARS-CoV-2 who died from various somatic diseases. HHV DNA and SARS-CoV-2 RNA were determined by PCR., Results: HHV DNA was found in autopsy samples from all patients. In group 1, EBV was most often detected in lymph nodes (94%), HHV-6 in liver (68%), CMV in lymph nodes (18%), HSV in brain (16%), VZV in lung and spleen (3% each). The detection rates of HHVs in both groups was similar. Important differences were found in viral load. In patients with COVID-19, the number of samples containing more than 1,000 copies of HHV DNA per 100,000 cells was 52.4%, in the comparison group - 16.6% ( p < 0.002). An association has been established between the reactivation of HSV and HHV-6 and the severity of lung damage. Reactivation of EBV correlated with increased levels of liver enzymes., Conclusion: Reactivation of HHVs in patients with fatal COVID-19 was associated with severe lung and liver damages, which indicates a link between HHV reactivation and COVID-19 deaths.

Introduction: When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic., Results and Conclusion: The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.

Aim. Evaluation of comorbid pathology in SARS-CoV-2 infected in cancer practice as a predictor of severe outcomes. Testing the COVID-19 risk assessment tool in oncology (CORONET), to predict the likely severity of COVID-19 course in cancer patients on inpatient treatment. Materials and methods. A retrospective analysis of 173 cancer patient disease stories was conducted. The study was conducted as part of the program of the World-Class Research Center “Digital Biodesine and Personalized Health Care” of the University of Sechenov, with participation in the ESMO-CoCARE Register project. Based on the ESMO COVID-19 and CAncerREgistry (ESMO-CoCARE) registry, taking into account the entered our patient sample (n=173), a COVID-19 risk assessment tool in oncology (CORONET) was developed. Results. Cancer patients with comorbid pathology have been shown to have an increased risk of COVID-19 course of the disease from this sample by CORONET (mean conclusion score CORONET 2.44 pointsseverity). Prognosis of probable severity of outcomes in cancer patients infected with SARS-CoV-2 depends on associated diseases. The presence of a history of ≥3 comorbid pathologies in COVID-19 patients was detected in 106 people (61.27%). 15 patients were included in the risk of severe course. Retrospective analysis obtained actual confirmation of the prognosis of severe course of the disease in this group followed by death in all these patients (71.42% of all deaths). Indicators such as low albumin levels, high levels of C-reactive protein and neutrophils showed high prognostic significance of the likely severity of coronavirus infection in cancer patients on inpatient treatment for COVID-19. The mortality rate of patients admitted with COVID-19 and cancer was 12.14%. Conclusion. The most informative predictors of severe outcomes in COVID-19 in inpatient cancer patients to assess the prognosis of disease severity are: number of comorbidities, age, NEWS2 scale, ECOG patient activity status, albumin level, C-reactive protein level and absolute neutrophil level. The benefits gained in the use of the online decision support tool CORONET are considered convincing not only during the decision-making phase of hospitalization, but also in cancer patients on inpatient treatment.

Relevance. It is known that the main trigger for the development of the pandemic was the genomic diversity of viruses. Meanwhile, we did not find any studies on the influence of population susceptibility on the complex process of evolutionary transformations of the SARS-CoV-2 virus and their interdependent variability during the development of the pandemic. Aim. The study of the interdependent variability of two heterogeneous populations interacting in the dynamics of the development of the COVID-19 pandemic - the virus population and the population. Materials and methods. The study was conducted in the city of Perm from 03/01/2021. (Beginning of sequencing of the SARS-CoV-2 virus in the territory) until 01.01.2023. In weekly dynamics, the following were studied: SARS-CoV-2 genomic diversity (molecular genetic study of 2521 samples of biomaterial from patients), seroprevalence of the population (366,804 blood sera were examined for the presence of IgG), morbidity, disease prevalence rate and mortality (according to official statistics). The interpretation of the results was carried out in accordance with the provisions of the theory of self-regulation of parasitic systems by V.D. Belyakov. Results and discussion. An analysis of the genomic diversity of the virus during the pandemic made it possible to distinguish 5 periods. Three periods were characterized by the homogeneity of the pathogen population, when the variants Alpha, Delta and Omicron circulated. Two periods were characterized by the simultaneous circulation of two variants of viruses due to the adaptation of the virus to the changed habitat. Thus, the circulation of the Alpha variant in a population heterogeneous in terms of susceptibility (the proportion of seropositive ones increased to 52%) caused mutational changes in the virus genome with the formation of high transmission properties and high pathogenicity (according to the theory of V.D. Belyakov, the phase of formation of an epidemic variant). The formation of the epidemic variant of the pathogen (Delta genovariant) occurred within 12 weeks, it dominated for more than 6 months, increasing the incidence by 2.8 times, mortality by 17.3 times (epidemic spread phase). The increase in the incidence and large-scale vaccination increased the seroprevalence of the population to 70% or more. The Delta variant begins to adapt to a new habitat with a high proportion of immune organisms, the formation of the Omicron genovariant with high transmission and evasion of the immune response is underway (the phase of formation of the pathogen reservation variant). The pathogen population is heterogeneous; Delta and Omicron circulate simultaneously. Morbidity increases by 2.9 times, RT by 1.3 times, and mortality decreases by 5.1 times. Omicron replaces the Delta genovariant within 5 weeks, mortality decreases, while maintaining the distribution coefficient (reservation phase). Conclusions. Interdependent variability of the virus and the susceptibility of the population determined the phase development of the pandemic.

Computer simulation has been used to identify peptides that mimic the natural target of the SARS-CoV-2 coronavirus spike (S) protein, the angiotensin converting enzyme type 2 (ACE2) cell receptor. Based on the structure of the complex of the protein S receptor-binding domain (RBD) and ACE2, the design of chimeric molecules consisting of two 22-23-mer peptides linked to each other by disulfide bonds was carried out. The chimeric molecule X1 was a disulfide dimer, in which edge cysteine residues in the precursor molecules h1 and h2 were connected by the S-S bond. In the chimeric molecule X2, the disulfide bond was located in the middle of the molecule of each of the precursor peptides. The precursors h1 and h2 modelled amino acid sequences of α1- and α2-helices of the extracellular peptidase domain of ACE2, respectively, keeping intact most of the amino acid residues involved in the interaction with RBD. The aim of the work was to evaluate the binding efficiency of chimeric molecules and their RBD-peptides (particularly in dependence of the middle and edge methods of fixing the initial peptides h1 and h2). The proposed polypeptides and chimeric molecules were synthesized by chemical methods, purified (to 95-97% purity), and characterized by HPLC and MALDI-TOF mass spectrometry. The binding of the peptides to the SARS-CoV-2 RBD was evaluated by microthermophoresis with recombinant domains corresponding in sequence to the original Chinese (GenBank ID NC&#95;045512.2) and the British (B. 1.1.7, GISAID EPI&#95;ISL&#95;683466) variants. Binding to the original RBD of the Chinese variant was detected in three synthesized peptides: linear h2 and both chimeric variants. Chimeric peptides were also bound to the RBD of the British variant with micromolar constants. The antiviral activity of the proposed peptides in Vero cell culture was also evaluated.

Docking and quantum-chemical methods have been used for screening of drug-like compounds from the own database of the Voronezh State University to find inhibitors the SARS-CoV-2 main protease, an important enzyme of the coronavirus responsible for the COVID-19 pandemic. Using the SOL program more than 42000 3D molecular structures were docked into the active site of the main protease, and more than 1000 ligands with most negative values of the SOL score were selected for further processing. For all these top ligands, the protein-ligand binding enthalpy has been calculated using the PM7 semiempirical quantum-chemical method with the COSMO implicit solvent model. 20 ligands with the most negative SOL scores and the most negative binding enthalpies have been selected for further experimental testing. The latter has been made by measurements of the inhibitory activity against the main protease and suppression of SARS-CoV-2 replication in a cell culture. The inhibitory activity \of the compounds was determined using a synthetic fluorescently labeled peptide substrate including the proteolysis site of the main protease. The antiviral activity was tested against SARS-CoV-2 virus in the Vero cell culture. Eight compounds showed inhibitory activity against the main protease of SARS-CoV-2 in the submicromolar and micromolar ranges of the IC50 values. Three compounds suppressed coronavirus replication in the cell culture at the micromolar range of EC50 values and had low cytotoxicity. The found chemically diverse inhibitors can be used for optimization in order to obtain a leader compound, the basis of new direct-acting antiviral drugs against the SARS-CoV-2 coronavirus.

Coronaviridae is a family of single-stranded RNA (ssRNA) viruses that can cause diseases with high mortality rates. SARS-CoV-1 and MERS-CoV appeared in 2002-2003 and 2012, respectively. A novel coronavirus, SARS-CoV-2, emerged in 2019 in Wuhan (China) and has caused more than 5 million deaths in worldwide. The entry of SARS-CoV-1 into the cell is due to the interaction of the viral spike (S) protein and the cell protein, angiotensin-converting enzyme 2 (ACE2). After infection, virus assembly occurs in Golgi apparatus-derived vesicles during exocytosis. One of the possible participants in this process is LAMP1 protein. We established transgenic Vero cell lines with increased expression of human LAMP1 gene and evaluated SARS-CoV-1 and SARS-CoV-2 production. An increase in the production of both viruses in LAMP1-expressing cells when compared with Vero cells was observed, especially in the presence of trypsin during infection. From these results it can be assumed that LAMP1 promotes SARS-CoV-1 and SARS-CoV-2 production due to enhanced exocytosis.

Aim. To study the course of COVID-19 (COronaVIrus Disease 2019) in elderly patients with acute myeloid leukemia (AML), to analyze risk factors for unfavorable outcome.Materials and methods. The paper presents our own experience in the treatment of elderly (age ≥65 years) patients with AML and concomitant coronavirus infection in the hematology departments of City Clinical Hospital No. 52 (Moscow) from March 2020 to June 2022. The diagnosis of COVID-19 was considered confirmed based on a positive result of the polymerase chain reaction of an oropharyngeal and nasopharyngeal swab for SARS-CoV-2 and/or a typical radiological picture on a computed tomogram of the lungs.Results. An analysis of clinical, laboratory and instrumental data of 59 patients (30 (51 %) men, 29 (49 %) women) with AML and COVID-19 was carried out. All patients were treated for COVID-19 in accordance with the Temporary guidelines “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)” of the Russian Ministry of Health. Median age was 71 (65-91) years. AML was first verified in 27 % of hospitalized patients; 12 % were in remission of the disease. A month before hospitalization, 36 % of patients received antitumor therapy, and 19 % of patients had refractory AML. 17 % of hospitalized patients received antitumor therapy with cytarabine in small doses for vital indications. Death was recorded in 64 % of cases, in 24 % the cause of death was severe COVID-19. The unfavorable outcome was influenced by addition of secondary bacterial flora, refractory AML course and elderly age of patients.Conclusion. Pre-exposure prophylaxis with monoclonal antibodies and vaccination of patients may be the main methods of preventing infection and severe course of COVID-19.

The aim of the work was to study the pathogenicity of newly emerging variants of SARS-CoV-2 on the model of the Syrian golden hamster.Materials and methods. We used the strains of SARS-CoV-2 virus related to the VOC circulating in the territory of the Russian Federation. The experiments were carried out on outbreed Syrian hamsters obtained from the nursery of the SSC VB “Vector”. The infectious titer of coronavirus in tissue samples collected from infected laboratory animals was determined on a Vero E6 cell culture. The Ct in RT-PCR was considered an additional parameter for monitoring the viral load in the samples. The severity of lung tissue damage in Syrian hamsters with COVID-19 was assessed by histological preparations.Results and discussion. 50 % infecting doses in case of the intranasal infection have been determined, histological analysis of lung tissues performed. The pathogenicity of various variants of the SARS-CoV-2 virus for the Syrian hamster has been evaluated, differences in infecting doses and pathological changes in the lungs have been revealed. SARS-CoV-2 viruses belonging to Beta genetic variant have the highest virulence, while Alpha variant has the lowest one when comparing the studied strains by the ID50 value. The Delta and Omicron variants have a matched ability to cause specific damage to the tissues of the respiratory tract, while being inferior only to the Beta variant. It has been demonstrated that Syrian hamsters are an adequate model for assessing the pathogenicity of the SARS-CoV-2 virus variants of concern. Variants of SARS-CoV-2 virus during intranasal infection has shown different degree of pathogenicity in the Syrian hamster model.

New variants of SARS-CoV-2 such as Omicron BA.2, BA.4/5, BA.2.12.1 and BA 2.75 are characterized by higher infectivity and the ability to escape virus-neutralizing antibodies against previous coronavirus variants. The S-trimer of BA.2 and its phylogenetic derivatives are characterized by a predominant Up-conformation, which facilitates the interaction with ACE2 on target cells and promotes the resistance to neutralizing antibodies. The immunity acquired from the infection with earlier strains is non-sterile for both early and later strains; the booster systemic immunization does not significantly affect the effectiveness of antiviral immunity, and its feasibility is currently being questioned. Studies of the mucosal immune response have shown that intranasal immunization with adenovirus vaccines provides more pronounced protective immunity than systemic reimmunization does. A promising approach is the creation of multivalent inhaled next generation vaccines containing immunoadjuvants that activate B- and T-cell mucosal immunity. Currently, a large number of intranasal vaccines are undergoing phase I/II trials, while the preclinical and preliminary clinical results indicate that this method of vaccination provides a better mucosal immune response at the entry site of the virus than systemic immunization does. This strategy may provide a long-term immune protection against the currently existing and yet unknown new strains of SARS-CoV-2.

Introduction. The emergence of new epidemiologically significant variants of SARS-CoV-2 has shifted emphasis to development of a live vaccine, which would be able to provide protection against a wide range of antigenic variants of the virus. The aim of the study was to obtain SARS-CoV-2 variants attenuated through cold adaptation and to provide their biological characterization. Materials and methods. The Dubrovka laboratory strain of SARS-CoV-2 and its variants were cultured on Vero and Calu-3 cells. The virus quantification was performed by virus titration in Vero cells and by real-time reverse transcription-polymerase chain reaction. SARS-CoV-2 virions were analyzed using transmission electron microscopy. Genome sequences of the virus were identified by nanopore sequencing. The attenuation (att) phenotype of SARS-CoV-2 variants was identified using Syrian hamsters as an animal model for COVID-19. Results. Cold-adapted (ca) SARS-CoV-2 variants Dubrovka-ca-B4 and Dubrovka-ca-D2 were produced by continued passaging of the Dubrovka strain in the Vero cell culture at the temperature being gradually decreased to 23C and by subsequent cloning. Up to 20 nucleotide substitutions and 18 amino acid substitutions were detected in genomes of ca-variants. Ca-variants, as distinct from the parent Dubrovka strain, actively replicated at 23C, while the Dubrovka-ca-D2 variant had a temperature-sensitive (ts) phenotype (did not replicate at 39C). Ca-variants of the virus replicated poorly at 37C in the Calu-3 human lung cell culture, which, along with the ts-phenotype, can be a marker of virus attenuation for humans. In the intranasally infected Syrian hamsters, ca-variants of the virus demonstrated an attenuation phenotype: they did not cause loss of appetite, fatigue, drowsiness, did not slow down weight gain, replicating much more slowly in the lungs and brain compared to the virulent Dubrovka strain. Conclusion. The obtained attenuated SARS-CoV-2 ca-variants, Dubrovka-ca-B4 and Dubrovka-ca-D2, should be studied further as candidate vaccine strains for a live attenuated vaccine against COVID-19.

Background. The ongoing pandemic of the novel coronavirus infection (COVID-19) draws attention to the significance of molecular and genetic monitoring of the SARS-CoV-2 spread among the population of the Russian Federation. The aim of the study was to analyze the dynamics of circulation of SARS-CoV-2 genetic variants in Russia. Materials and methods. The analysis of the circulation dynamics for SARS-CoV-2 genetic variants in Russia was carried out, covering the period from 28/12/2020 to 26/6/2022. The analysis included the data from Rospotrebnadzor Report No. 970 "Information about Infectious Diseases in Individuals with Suspected Novel Coronavirus Infection" and the Virus Genome Aggregator of Russia (VGARus). The presence of SARS-CoV-2 RNA was confirmed by the real-time reverse transcription polymerase chain reaction. The primer panels developed at the Central Research Institute of Epidemiology were used for amplification of genomic fragments and the subsequent sequencing. Results and discussion. Using the Russian VGARus platform developed by the Central Research Institute of Epidemiology, we received the data on mutational variability of SARS-CoV-2. By monitoring the circulation of SARS-CoV-2 genetic variants in Russia from 28/12/2020 to 26/6/2022, we found that Delta and Omicron genetic variants prevailed at different stages of the epidemic. Conclusion. The data of molecular and genetic studies are an essential component of epidemiological surveillance, being critically important for making executive decisions aimed at prevention of further spread of SARS-CoV-2 and laying the groundwork for creating new vaccines.

Relevance. The long-term leadership of ARVI pathogens determines their significance in the damage caused to both health and the economy of the country. Aim. To identify the features of the structure of ARVI during the emergence and widespread spread of SARS-CoV-2. Materials and methods. The article uses methods used in epidemiological surveillance of acute respiratory viral infections. Results and discussion. The results of the diagnostic available ARVI pathogens monitoring during epidemic seasons 2018-2021 are presented. The tendency of greater engagement of aged group 15 y.o. and older in epidemic process by morbidity and hospitalization due to SARI was shown. 49 818 nasal swabs from patients with influenza infection, 36 044 – with ARVI and 59 062 – with SARS-CoV-2 were tested. The top three in the structure of ARVI were INF, HEV-D and HRSV (in the 2018–2019 season); INF, SARS-CoV-2 and HEV-D (2019–2020); SARS-CoV-2, HEV-D and HPIV/HCoV (2020–2021). The activity of viral pathogens also differed: for HPIV, HAdV, HEV-D, HMPV, a decrease in activity was noted during the appearance of SARS-CoV-2 (2019–2020) and some of its growth in the following season; in relation to HRSV and INF - a decrease in activity during the last two seasons, and for INF – extremely low activity in the 2020-2021 season; the activity of seasonal HCoV even increased slightly. The data of genetic analyses of SARS-CoV-2 positive samples showed the heterogeneity of its population with a representative of variants (Alfa, Delta) as well as endemic for Russia and Moscow variants only. The recommended composition of influenza virus vaccines for use in the 2021–2022 northern hemisphere influenza season and in the 2022 southern hemisphere influenza season are presented due to their drift changeability. Conclusions. SARS-CoV-2 was influenced by the activity of ARVI pathogens with the almost complete displacement of influenza viruses from the circulation in the period 2020–2021.

Relevance. The problem of timely and effective diagnosis of COVID-19 remains one of the main problems facing healthcare. In this regard, the task of developing test systems for the etiological diagnosis of COVID-19 remains extremely relevant. Purpose To develop ELISA test system for detection of G specific immunoglobulins to SARS-COV-2 coronavirus by immunoblotting (Line Blot). Methods. Elaboration of techniques for obtaining test components and preliminary assessment of its diagnostic effectivenessin blood serums from COVID-19 patients treated at N. I. Pirogov First Gradsky Hospital, Moscow, and serums from healthy human donors. Results. The study of 104 blood serum samples from COVID-19 patients and 100 blood serum samples from healthy human donors, pre-tested by ELISA IgG to SARS-CoV-2 using «Vitrotest SARS-CoV-2 IgG» test systems (Vitrotest, Ukraine) and «ELISA-SARS-CoV-2-AB-G» (CJSC EKOlab, Russia) showed high diagnostic efficiency of the new test system. Conclusion. The new test system after state registration of the medical device can be recommended as a confirmatory test for the etiological laboratory diagnosis of COVID-19.

Nowadays, the most notable negative effects of SARS-CoV-2 are the pulmonary manifestations as well as cardiovascular system damage. Evaluation of postvaccination changes in the male reproductive system and analysis of their mechanisms seem to be important because of their direct effect on fertility. Thus, it may play a significant role in perspective. Studies based on the application of fluorescence in situ hybridization showed that most acini epithelial cells, as well as some mesenchymal and endothelial cells were positive for SARS-CoV-2 RNA. As for co-expression of the ACE2 cell receptor and the serine protease TMPRSS2, which the virus uses to enter cells, it was also detected in most prostate epithelial and stromal cells. The mechanism of prostate damage in COVID-19 may also be related to dysregulation of the renin-angiotensin system. Increased levels of angiotensin-2 secretion in the prostate in patients with benign prostatic hyperplasia may increase the effect of the virus directly on the cells of the organ. These mechanisms may explain the elevated serum prostatic specific antigen levels in patients with benign prostatic hyperplasia during the active period of COVID-19. Non-specific mechanism of prostate damage is connected with coagulopathy development – thrombosis of venous plexus and hemodynamic disturbances, which can cause secondary damage of parenchyma. There is a definite relationship between the hormonal status of the patient and the severity of the infection – low levels of both testosterone and dihydrotestosterone contribute to the development of severe complications in patients infected with SARS-CoV-2. The possibility of using testosterone drugs in patients with hypogonadism and COVID-19 as an alternative treatment option – to suppress the cytokine storm phenomenon – is being considered. Patients with a history of prostate cancer, with localized prostate cancer in the absence of metastases participated in vaccine studies – among the side effects of vaccination in several cases only regional lymphadenopathy on the injection side of the drug was noted.

This article presents current data on the impact of COVID-19 (SARS-CoV-2) on pregnancy and perinatal consequences. The working theories of the pathogenesis of obstetric and fetal complications due to infection during pregnancy, already proven to date, are considered. Symptoms of COVID-19 disease, the risk of their development, and frequency of severe disease in non-pregnant and pregnant women of reproductive age do not differ significantly. However, there are powerful studies that have shown that this infection in pregnant women leads to a high probability of a dramatically severe and fulminant course. Pregnant women with SARS-CoV-2 infection have an increased risk of preeclampsia, incl. severe, hemolysis, thrombocytopenia and increased levels of liver enzymes compared with pregnant women without infection. Women who have COVID-19 are twice as likely to have preterm rupture of the membranes and three times as likely to have a preterm birth compared to the not infected pregnant women. Vertical transmission of the virus from mother to fetus is likely, but data are insufficient to be certain. There is also insufficient evidence of an increased miscarriage rate and teratogenic effects of the COVID-19 virus. However, antenatal fetal death is statistically significantly more common in infected pregnant women than in uninfected pregnant women. Morphological and functional disorders in the chorion/placenta are the main pathogenetic factor in the development of preeclampsia, intrauterine growth retardation, antenatal fetal death and impaired state of the fetus and children born by women with COVID-19. Many studies report that mothers with confirmed COVID-19 infection has asymptomatic babies. At the same time, some studies indicate adverse complications in newborns from infected mothers. The most common neonatal disorders in babies from pregnant women with COVID-19 are tachypnea, hyperthermia, and gastrointestinal disorders, in particular vomiting and flatulence.

Introduction: The study of the mechanisms of transmission of the SARS-CoV-2 virus is the basis for building a strategy for anti-epidemic measures in the context of the COVID-19 pandemic. Understanding in what time frame a patient can spread SARS-CoV-2 is just as important as knowing the transmission mechanisms themselves. This information is necessary to develop effective measures to prevent infection by breaking the chains of transmission of the virus. The aim of the work is to identify the infectious SARS-CoV-2 virus in patient samples in the course of the disease and to determine the duration of virus shedding in patients with varying severity of COVID-19., Materials and Methods: In patients included in the study, biomaterial (nasopharyngeal swabs) was subjected to analysis by quantitative RT-PCR and virological determination of infectivity of the virus., Results: We have determined the timeframe of maintaining the infectivity of the virus in patients hospitalized with severe and moderate COVID-19. Based on the results of the study, we made an analysis of the relationship between the amount of detected SARS-CoV-2 RNA and the infectivity of the virus in vitro in patients with COVID-19. The median time of the infectious virus shedding was 8 days. In addition, a comparative analysis of different protocols for the detection of the viral RNA in relation to the identification of the infectious virus was carried out., Conclusion: The obtained data make it possible to assess the dynamics of SARS-CoV-2 detection and viral load in patients with COVID-19 and indicate the significance of these parameters for the subsequent spread of the virus and the organization of preventive measures.

Studiul a prevăzut evaluarea rezultatelor tratamentului ischemiei acute (IA) a extremităților la pacienții cu infecție cu coronavirus de tip nou (COVID-19). Lotul a inclus 62 pacienți; 67 extremități: superioare - 19 (28,3%), inferioare - 48 (71,6%). Repartizarea cazurilor în funcție de gradul IA (Rutherford): I - 7 (10,4%), IIA - 10 (14,9%), IIB - 34 (50,7%), III - 16 (23,8%). COVID-19 s-a confirmat prin testul polymerase chain reaction , la 45 (72,5%) pacienți fiind documentată afectarea pulmonară. Tratamentului chirurgical au fost supuși 50 (80,6%) pacienți; 52 membre. Rata amputațiilor pe durata spitalizării (9,4±9 zile) - 19,4%; rata decesului - 43,5%, fiind influențată semnificativ de prezența sau absența afectării pulmonare - 55,5% vs. 11,7% (P=0,002; testul χ²). Potențial predictiv al mortalității au manifestat biomarkerii: proteina C reactivă/albumina, trombocite/limfocite, fibrinogen/albumina. Către follow-upul de 21 (25%-75%IQR 19-28) luni supraviețuirea generală și fără amputații: 56,4% și 57,1%, corespunzător.

Aim. To analyze the lipid profile changes during the acute phase of coronavirus disease 2019 (COVID-19) and within 12 months after discharge from the hospital (post-Covid period) in comparison with the lipid profile of patients before COVID-19.Material and methods. The subanalysis of the registry was carried out as follows: clinical investigators in each of the centers included patients in the AKTIV registry selected from the database patients who met three following criteria: (1) availability of lipid profile test no more than 60 days before COVID-19; (2) availability of lipid profile test during the acute period; (3) availability of lipid profile test within 6-12 months after discharge from the hospital.Results. In patients after COVID-19, a decrease in the levels of all lipid profile parameters in the acute COVID-19 phase and their subsequent increase were found.In the post-COVID-19 period, 25,7% of patients experienced an increase in lipid profile parameters (increased levels of total cholesterol (TC) and/or cholesterol, low-density lipoproteins and/or triglycerides and/or cholesterol excluding high-density lipoproteins by ≥0,5 mmol/l) despite the fact that lipid-lowering therapy in these patients was at least no worse than in patients without lipid profile changes.Multivariate analysis found that such variables as age (direct relationship), body mass index (direct relationship), estimated glomerular filtration rate in the acute phase (inverse relationship) and cholesterol level excluding high-density lipoproteins in the acute period (inverse relationship), as well as heart failure, obesity and cytokine storm in the acute COVID-19 phase are independent predictors of an increase in one or more lipid parameters by ≥0,5 mmol/l over 6-12 months of post-COVID-19 period.Conclusion. COVID-19 likely contributes to the onset and/or progression of lipid metabolism disorders in COVID-19 survivors (Eurasian population).

Background The novel coronavirus disease-2019 (COVID-19), which is caused by Severe Acute Respiratory Distress Syndrome coronavirus 2 (SARS-CoV2), was originally detected in Wuhan, China in December 2019. In this meta-analysis and literature review, we compared and summarized the clinical presentation, cerebrospinal fluid (CSF) and electromyography (EMG) findings and outcomes in SARS-CoV-2 patients with Guillain-Barre Syndrome (GBS) and its variants. Methods We conducted a literature review in February 2023 searching for terms “Guillain-Barre Syndrome and COVID-19", “SARS neurology”, “COVID-19 complications”. We used PubMed and Google Scholar databases inquiring case reports or series of cases published between April 1, 2020, and September 14, 2023. Results Of the 52 GBS cases 61,5% (n=32) were male and 39,5% (n=20) were female. The mean age was 57 years old. A total of 75% (n=33) patients presented acute inflammatory demyelinating polyneuropathy (AIDP) variant, 6,8% (n=3) presented acute motor axonal neuropathy (AMAN) variant, 15,9% (n=7) presented acute motor-sensory axonal neuropathy (AMSAN) variant. A total of 85,7% (n=42) of patients were diagnosed with albuminocytological dissociation. During the hospitalization, a total of 30,8% (n=16) required mechanical ventilation. A total of 61,5% (n=32) of patients were treated with a 5-day regimen of intravenous immunoglobulin (IVIG) in dose 0.4 g/kg/day. There were 46,1% (n=24) complete recoveries from GBS, 32,7% (n=17) partial recoveries and 9,6% (n=5) of patients did not respond to treatment. A total of 11,5% (n=6) of patients died. Conclusion It is crucial to follow patients with COVID-19 and GBS over time to estimate properly the efficacy of treatment and evaluate the real percentage of recovery and complications.

Since the onset of the SARS-CoV-2 infection, there has been an increase in the number of reports of patients who have experienced the development of autoimmune neurological disorders. It is assumed that such an increase in the incidence rate may occur due to an abnormal immune-mediated response of the body to the pathogenic impact of SARS-CoV-2. This article discusses the possibility of the influence of SARS-CoV-2 on the onset and exacerbation of the course of autoimmune neurological disorders, possible pathogenetic factors and mechanisms, and analyzes the features of the clinical picture and therapy. The article includes foreign and Russian scientific data and clinical observations of cases of Guillain-Barré syndrome, multiple sclerosis, acute disseminated encephalomyelitis, myasthenia gravis and other autoimmune diseases that have changed their typical course on the background of COVID-19.

Objective: development and validation of a reverse transcription polymerase chain reaction (RT-PCR) test kit for SARS-CoV-2 ribonucleic acids (RNA) qualitative detection adapted for using with automated station for RNA extraction.Material and methods. Assessment of clinical performance was carried out on biological samples (nasal and oropharyngeal swabs and sputum) obtained during the diagnostic procedure. The presence of novel coronavirus RNA was established using a reference kit. Sensitivity was evaluated on standard SARS-CoV-2 sample (EDX SARS-CoV-2 Standard, Bio-Rad Laboratories, USA).Results. Presence of SARS-CoV-2 RNA is detected by two genome regions. Sensitivity determined by testing SARS-CoV-2 standard was 250 copies/ml. Coefficient of variation during the testing of samples with the concentration of 104 copies/ml did not exceed 5% in different conditions. Diagnostic sensitivity against reference test was 100% (95% confidence interval (CI) 95.6–100) for nasal and oropharyngeal swabs and 100% (95% CI 94.8–100) for sputum. Diagnostic specificity was 100% (95% CI 95.6–100) for nasal and oropharyngeal swabs and 100% (95% CI 94.8–100) for sputum. The turnaround time for test from RNA extraction till obtaining results was about 3 hours when testing 96 samples using automated stations for RNA extraction.Conclusion. Using the kit together with automated station for RNA extraction will increase laboratory testing capacity in pandemic conditions.

The purpose of the research was to study the dynamics of residual infectious activity of SARS-CoV-2 virus strains belonging to different genovariants, on different types of surfaces, in samples of drinking dechlorinated water at 24–28 °C, as well as their resistance to disinfectants.Materials and methods. The studies were carried out using SARS-CoV-2 coronavirus strains obtained from the State Collection of Causative Agents of Viral Infectious Diseases and Rickettsiosis, which operates at the premises of the SSC VB “Vector”. The evaluation of the residual infectivity of the SARS-CoV-2 coronavirus was carried out through titration of samples in cell culture.Results and discussion. The conducted studies have confirmed the ability of all investigated strains of the SARS-CoV-2 coronavirus to maintain their infectious activity at 24–28 °C on most of the examined types of test surfaces for at least 48 hours, while the virus is best preserved on stainless steel and plastic. All studied strains of the SARS-CoV-2 coronavirus are viable in drinking dechlorinated water for at least 48 hours. In addition, it has been found that all of them are sensitive to disinfectants of different groups, widely used for disinfection when working with pathogenic biological agents or for treating hands and surfaces contaminated with viruses. Chlorine-containing disinfectants are the most active. Skin antiseptics based on ethyl and isopropyl alcohols are suitable for disinfecting hands and objects contaminated with the SARS-CoV-2 virus.

Background: The global pandemic of coronavirus disease is a societal, economic, and publichealth crisis that is still underway. The spike glycoprotein of SARS-CoV-2 is one of the primary ingredients for virulence, tissue tropism, and host areas. Aim: This study aimed to determine mutations in the S protein of the Iraqi COVID-19 isolates.Full genome sequences of Iraqi strains were obtained from GISAID. Using statistical saturation mutagenesis and other informatics methods, we investigated 20 sequences of SARS-CoV-2 S protein missense mutation isolates in Iraq selected from NCBI.The following mutations were detected for all the strains under study compared to the wild type: L452R, A522V, E583D and D614G. The number of mutations in the strains was different depending on the location of the state from which the sample was collected The D614G mutation was found in 19 strains. One strain had three mutations, while the other was a wild form strain. The structure of the mutant protein changes dramatically, as does the energy of the atoms concerning the docking position, affecting the protein's stability.The mutation sites would improve the S protein's stability. Molecular docking of RBD-ACE2 is affected differently by residues L452R and A522V.

The COVID-19 pandemic has produced its effects on functioning of all the state institutions, the public healthcare system being a peculiar one among them. Medical personnel have become an unprotected population group that was actively involved into the epidemic process. Results produced by several studies indicate that relative risks to become infected with COVID-19 are by up to 11.6 times higher for medical personnel than in population at large. A share of medical personnel among patients with COVID-19 varies in different countries, from 4.2 % in China to 17.8 % in the USA. According to official statistics, in 2020 a share of medical personnel who became infected with COVID-19 in in-hospital foci amounted to 68.6 % in the RF regions located in the Urals and Siberian Federal Districts. High epidemic potential of the virus and intensive mass contacts between medical personnel and their patients make for rapid SARS-CoV-2 spread and infection among them. It is vital to examine all the range of risk factors that cause SARS-CoV-2 infection among medical personnel. The present study involved using “The map of epidemiological investigation focused on the incidence of the new coronavirus infection (COVID-19) in medical personnel”. The map was located on Google Cloud Platform. Overall, 613 medical workers from different medical organizations took part in the research. We applied sociological, epidemiological and statistical research techniques. We established that work in an infectious diseases hospital increased a relative risk of SARS-CoV-2 infection by 1.8 times (RR = 1.78; 95 % CI [1.65–1.93]). The total risk of SARS-CoV-2 infection was insignificant for workers employed at a medical organization that provided scheduled medical assistance to population (RR = 1.02; 95 % CI [1.00–1.04]). However, certain factors created elevated risks of infection. Any contacts with COVID-19 patients who were close relatives, friends or neighbors were established to be significant (RR = 1.13; 95 % CI [1.04–1.228]). The research results should be used when organizing work procedures and anti-epidemic activities in infectious diseases hospitals and medical organizations providing scheduled assistance to population. The focus should be on providing medical personnel with personal protective equipment as well as on calculating relevant duration of a work shift relying on the risk-based approach.

Relevance. The formation of humoral immunity is one of the most important manifestations of the protective mechanism against an infectious disease. The formation of antibodies with neutralizing activity is a key factor in preventing infection.Aims. Analysis of the esults of an ELISA study for the presence of IgM and IgG antibodies to the causative agent of a new coronavirus infection (COVID-19) in the population of the Central Orenburg region.Materials and methods. Immunoassay of blood serum for the presence of IgM and IgG antibodies using ELISA test by Vectro-Best (Novosibirsk, Russia).Results and discussion. The analysis revealed the presence of more than half of the cases of seroconversion among the examined individuals. The most surveyed was the group aged 21 to 65 years. The most typical humoral immune response to SARS-CoV-2 has been established, and the age-related characteristics of its formation have been determined. The dependence of the positivity coefficient on the age of the patients was revealed.Conclusions. According to the results of the study, the formed humoral (collective) immunity to the SARS-CoV-2 virus was registered in more than half of the studied sample.

Aim: To identify the features of plasma, platelet hemostasis, and proteomic composition of the blood plasma in patients with acute myocardial infarction (AMI) and healthy volunteers after COVID-19., Material and Methods: The study included patients with AMI who have recently had COVID-19 (AMI-post-COVID, n=56) and patients with AMI who have not recently had COVID-19 (AMI-control, n=141). Healthy volunteers constituted the control groups and were also divided into control-post-COVID (n=32) and control-control (n=71) groups. Previous SARS-CoV-2 infection was determined by anti-N IgG in the blood serum, the level of which persists for 6-10 months after the disease. Hemostasis was evaluated by thromboelastometry (on whole blood), thrombodynamics (on platelet-poor plasma), fibrinolysis, impedance aggregometry, and proteomic analysis., Results: The AMI-post-COVID and AMI-control groups had higher values of thrombus growth rate, size and density based on the data of thromboelastometry and thrombodynamics, as well as increased concentrations of the complement system components, proteins regulating the state of the endothelium, and a number of acute-phase and procoagulant proteins compared to the control groups. Furthermore, in the AMI-post-COVID group, compared to the AMI-control group, the thrombus density was lower, and its lysis rates were higher when measured by the thrombodynamics method on platelet-poor plasma, while the platelet aggregation induced by ADP and thrombin was higher. Also, in the control-post-COVID group, compared to the control-control group, the thrombus formation rate was lower, whereas, in contrast, the thrombus size as measured by the thrombodynamics method and the platelet aggregation induced by arachidonic acid and thrombin were higher. In addition, in the AMI-post-COVID group, compared to the AMI-control group, the concentrations of proteins involved in inflammation and hemostasis were lower., Conclusion: Patients with AMI who have recently had COVID-19 are characterized by a less pronounced activation of the immune response compared to patients with AMI who have not had COVID-19. This may be due to long-term chronic inflammation and depletion of components of the immune activation system after SARS-CoV-2 infection. Long-term activation of the hemostasis system in both patients with AMI and healthy volunteers after COVID-19 is primarily due to the platelet component of hemostasis.

Background: Patients with diabetes mellitus (DM) are at risk for a higher incidence and severity of COVID-19, as well as its adverse outcomes, including post-Covid syndrome., Aim: to assess the incidence of cardiorenal complications in patients with type 1 and type 2 diabetes (T1DM/T2DM) who have had COVID-19, and to analyze the structure and severity of disorders according to examination data at the Diamobil mobile medical diagnostic and treatment center., Materials and Methods: a cohort of T1DM and T2DM patients examined in Diamobil (n=318), with a confirmed anamnesis of COVID-19 (n=236). The time interval between COVID-19 and the visit to Diamobil was 8.7/8.2 months for T1DM/T2DM. The parameters of the last visit before COVID-19 recorded in the Federal Register of Diabetes (FRD) were used as initial data., Results: Clinical characteristics of patients with T1DM/T2DM: age - 49.2/64.5 years, duration of DM - 22/11 years, proportion of women - 64/73%, respectively. After analysis the data from visits before and after COVID-19 there weren't statistically significant differences in HbA1c levels for both types of DM (before 9.0/8.3%; after 8.4/8.2%, respectively), there was the intensification of glucose lowering therapy (the proportion of patients with T2DM on 2 and 3 component therapy increased by 4.3% and 1.6%, the proportion of patients on insulin therapy by 16%). After COVID-19, there was a statistically significant decrease in glomerular filtration rate (GFR) in T1DM from 88.1 to 62 ml/min/1.73 m2; with T2DM from 74.7 to 54.1 ml/min/1.73 m2. When assessing acute diabetic complications, there was an increase in the frequency of coma in T1DM by 1.5 times, severe hypoglycemia in T1DM by 3 times, and in T2DM by 1.7 times. Analysis of the frequency of cardiorenal complications before and after COVID-19 showed a total increase of 8.5% in T1DM, by 13.2% in T2DM, of which myocardial infarction, ischemic heart disease, and CHF increased in T1DM in the range from 1.5 to 5 times, with T2DM by 1.3 times, the frequency of CKD with T1DM by 1.5 times, with T2DM by 5.6 times., Conclusion: There was a decline of kidney filtration function (decrease in GFR) and an increase in the frequency of cardiovascular complications in both types of diabetes in post-Covid period while patients achieved a stable HbA1c levels by intensifying therapy during the COVID-19 infection. This fact reflects combined damage to the kidney and cardiovascular system as a part of the post-Covid syndrome and determines a key set of measures for the development of preventive strategies.

Aim. Clinical case report of multisystem inflammatory syndrome, probably associated with COVID-19 and complicated by large thrombus in the right atrium in a child highlights the problems of monitoring, treatment, and the possibility of their solution. Presentation of a clinical case. We demonstrate one of the cases of multisystem inflammatory syndrome (MIS-C), which meets WHO criteria. In a child with a severe course of the disease and symptoms of hyperinflammation, on the 16th day from the onset of the disease, a positive effect was registered on the introduction of human normal immunoglobulin for intravenous administration and glucocorticosteroids. But on the day 27 of the disease, despite administration of anticoagulant therapy, a large blood clot was found in the right atrium cavity. Operation was performed with removal of the thrombus from the right atrium under artificial blood circulation and the child was discharged in satisfactory condition to continue treatment in an outpatient setting on the day 56 of the disease. Conclusions. Timely diagnosis of MIS-C in children with fever, signs of inflammation and organ dysfunction during the pandemic spread of COVID-19 and reasonable administration of intravenous immunoglobulin and steroids may reduce the inflammatory response and improve the prognosis. It is also important to conduct population-based prospective studies to optimize thromboprophylaxis in children with COVID-19 and MIS-C.

We present a clinical observation of a patient whose cause of death was a new coronavirus infection COVID-19 complicated by bilateral viral interstitial pneumonia and adult acute respiratory distress syndrome. The presence of background diseases-rheumatoid arthritis and secondary AA-adrenal amyloidosis-worsened the prognosis. Waterhouse-Friderichsen syndrome with hemorrhage and foci of necrosis in the adrenal cortex developed against a background of SARS-CoV-2 infection. The unique feature of this case is the long-term favorable course of the disease and its rapid progression after infection with SARS-CoV-2. The associated syndrome of disseminated intravascular coagulation further aggravated the patient's condition.

Countering the spread of new respiratory infections and reducing the damage they cause to society requires efficient strategies for rapidly developing of targeted therapeutics, such as monoclonal antibodies. Nanobodies, defined as variable fragments of heavy-chain camelid antibodies, have a set of characteristics that make them particularly convenient for this purpose. The speed at which the SARS-CoV-2 pandemic spread confirmed that the key factor in the development of therapeutics is obtaining highly effective blocking agents as soon as possible, as well as the diversity of epitopes to which these agents bind. We have optimized the selection process of blocking nanobodies from the genetic material of camelids and obtained a panel of nanobody structures with affinity to Spike protein in the lower nanomolar and picomolar ranges and with high binding specificity. The subset of nanobodies that demonstrate the ability to block the interaction between the Spike protein and the cellular ACE2 receptor was selected in experiments in vitro and in vivo. It has been established that the epitopes bound by the nanobodies are located in the RBD domain of the Spike protein and have little overlap. The diversity of binding regions may allow a mixture of nanobodies to retain potential therapeutic efficacy towards new Spike protein variants. Furthermore, the structural features of nanobodies, particularly their compact size and high stability, indicate the possibility of their utilization in the form of aerosols.

Aim. In vitro analysis of the inhibitory activity of aqueous extracts of ready‐made tea compositions and their constituent ingredients on SARSCOV‐ 2 replication.Material and Methods. The laboratory strain SARS‐CoV‐ 2/human/RUS/Nsk‐FRCFTM‐1/2020 was passivated on Vero cell culture. For the preparation of water extracts six types of experimental tea compositions (not containing flavorings) based on black and green tea or flowers of hibiscus as well as individual ingredients were used. Antiviral (inhibitory) activity of plant raw materials was studied in vitro according to the classical scheme of neutralization (inactivation) of the virus.Results. When compared with the main control sample of an aqueous extract of chaga (Inonotus obliquus) with a 50% effective concentration equal to 13.72±2.99 μg/ml against 103 TCPD50/ml of SARS‐CoV‐2, superior activity was found for extracts of the spice Syzygium aromaticum L. and black tea from Nepal. Approximately equal inhibitory activity was detected for extracts of tea compositions based on black tea with the addition of the grass Thymus altaicus and the spice S. aromaticum L. or with the addition of seeds of Carum carvi L. and the root of Angelica archangelica L. In addition, such activity was detected for extracts of tea compositions based on green tea from China with the addition of leaves of Mentha piperita L. and flowers of Lavandula angustifolia MILL. or with the addition of the peel of Citrus sinensis L. and seeds of Pimpinella anisum L. Extracts from individual plant raw materials used to make tea compositions were black teas from India, Argentina, Vietnam and Sri Lanka, leaves of M. piperita L. and flowers of L. angustifolia MILL. Cetraria islandica lichen, green tea and berries of Oxycoccus also showed antiviral activity.Conclusion. The results obtained suggest that tea compositions based on black and green tea with the addition of various plant raw materials in the form of a regular drink can be useful to people with COVID‐19 infection.

Despite the rapid accumulation of facts about the humoral immune response in COVID-19, there are still no evidencebased answers to questions about the factors influencing the level and duration of the detection period of antibodies to SARS-CoV-2 in the blood.Objective: To assess the prevalence, clinical and demographic associations of IgG antibodies to RBD of the SARSCoV-2 spike protein at different times after COVID-19.Materials and methods. Residents of the Altai region of Russia, Caucasians aged 20-93 years, who had COVID-19 from May 2020 to February 2021 (n = 314), took part in a onetime observational study. The level of antibodies in the blood was measured by enzyme-linked immunosorbent assay 1-14 months after the onset of the clinical manifestation of COVID-19.Results. Anti-RBD IgG antibodies of the SARS-CoV-2 spike protein were detected in 86.9% of the study participants. The dependence of the antibody titer on the duration of the period after COVID-19 was not revealed. The antibody titer was positively correlated with the complication of COVID-19 pneumonia and the volume of lung tissue lesions. The presence of pneumonia COVID-19 and the volume of lung tissue lesions are positively associated with age. Age positively correlated with antibody titer regardless of the pneumonia COVID-19 in the anamnesis.Conclusion. IgG antibodies to RBD of the SARS-CoV-2 spike protein are present in most of the COVID-19 patients. The titer of these antibodies in adults depends on age, complications of pneumonia COVID-19, and probably persists up to 14 months after the first symptoms of infection appear.

Aim: to evaluate the efficacy and safety of convalescent plasma therapy for patients with severe SARS-CoV-2 infection.Materials and methods: the study included 64 patients with laboratory-confirmed severe new coronavirus infection. The control group consisted of 58 patients who, in addition to standard therapy, received a transfusion of plasma from donors who had recovered from COVID-19. The effectiveness of immune plasma was assessed by the duration of fever, the level of oxygen (SpO2 %) in dynamics, the detection of SARSCoV-2 RNA in nasopharyngeal and oropharyngeal swabs using PCR method in dynamics, as well as by the dynamics of blood tests results. Adverse events (any medically adverse events that occurred after immune plasma transfusion) were recorded as safety criteria.Results: patients who received convalescent plasma, showed a significantly shorter period of SARS-CoV-2 replication compared with the control group. The use of immune plasma did not have a statistically significant effect on the duration of the fever, as well as the dynamics of blood oxygenation. Also, there were no significant differences compared with the control group when assessing blood tests parameters.Conclusion: The use of COVID-19 convalescent plasma to treat severe COVID-19 did not show significant clinical effect but reduced the period of viral replication. It also showed no unexpected or serious adverse events.

Background. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has one of the largest genomes. It encodes 16 non-structural proteins that are necessary for replicating and overcoming host defense mechanisms. Flavonoids are of interest as research objects in developing drugs for comprehensive COVID-19 therapy. This group of compounds is characterized by a wide range of biological activity and a high safety profile.Aim. To perform virtual screening of flavonoids for possible inhibition of proteins of the SARS-CoV-2 infection.Materials and methods. Structural proteins of SARS-CoV-2 infection, such as ADP-binding domain NSP3, main protease NSP5, RNA-dependent RNA-polymerase NSP12, and endoribonuclease NSP15, were obtained from Protein Data Bank (PDB). Flavonoid structures were obtained from the ZINC database. Protein models were processed using AutoDockTools software, and ligands were processed in Raccoon | AutoDock VS. Virtual screening and re-docking were performed in AutoDock Vina.Results. Validation showed agreement between native and re-docked conformations, indicating the applicability of the virtual screening method. Flavonoids interacted with the key amino acid residues in all the studied proteins. The highest binding energy was demonstrated by 3,7-dihydroxyflavone and 6S-coccineone B, the latter having a multimodal effect.Conclusion. The results of the study may be used for the development of phytomedicines for comprehensive therapy for COVID-19.

Introduction. Morbidity and mortality of COVID-19 actualizes the identification of groups with the greatest risk of primary and re-infection, persons in need of priority vaccination or revaccination.Objective. To study the factors affecting the content of IgG antibodies to the S-protein SARS-CoV-2 in convalescents after suffering COVID-19 for 6 months.Materials and methods. The study of the Military Medical Academy and the Helix Laboratory Service was carried out from 06/01/2020 to 08/01/2021 on the basis of the Military Medical Academy and the Helix centers. The study included 1421 people – both sexes from 18 to 70 years old. 1205 with asymptomatic and mild disease (outpatient group). 216 with moderate or severe form (inpatient group). The outpatient group underwent a quantitative determination of IgG to the spike (S) protein SARS-CoV-2 by immunochemiluminescence analysis at 30, 45, 60, 90, 180 days from diagnosis. The diagnosis was verified by a positive RT-PCR result. The inpatient group underwent an identical study on the 1st, 14th, 45th, 60th, 90th and 180th days from the moment of admission to the hospital. The diagnosis was verified in the same way.Results. In convalescents, post-infectious immunity is formed from 30 days. Older age was associated with a more pronounced production of IgG to the S-protein SARS-CoV-2, mainly in older women. Moderate and severe course is characterized by higher concentrations of IgG to the SARS-CoV-2 S protein. A high level of IgG to the S-protein SARS-CoV-2 persists for up to 90 days, with a subsequent decrease by 180 days. Body weight, days of oxygen therapy, hyperthermia, the volume of lung tissue lesions and the level of C-reactive protein correlate with the concentration of IgG to the S-protein SARS-CoV-2. The use of glucocorticoids (GCS) is characterized by the presence of a higher concentration of IgG to the S-protein SARS-CoV-2 up to 6 months. There is a dose-dependent effect of using GCS.Conclusion. The formation and maintenance of the level of neutralizing antibodies for 6 months depends on the severity of the disease, the gender and age of the patients, and the fact of using GCS. This must be taken into account when carrying out therapeutic and preventive measures, planning vaccination.