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According to international research data, COVID-19 increases the risk of developing hypertensive and metabolic disorders. Aim of the study was to assess the risks of hypertensive and metabolic disorders in pregnant women with COVID-19 and to identify potential markers of these conditions. Material and methods. The study involved 265 pregnant women, infected in the first, second, and third trimesters of pregnancy, and uninfected with COVID-19, from 2020 to 2022. Spectrophotometric methods were used to evaluate blood level of glucose, total cholesterol, high- and low-density lipoprotein (LDL), and triglycerides. ELISA was used to measure content of oxidized LDL and apolipoprotein B (apo B). Results. Gestational arterial hypertension (GAH) developed more frequently in women with COVID-19 infected in the second trimester compared to those infected in the third trimester (15.7 and 6.1 % cases, respectively, p = 0.044). Gestational diabetes mellitus (GDM) was more commonly diagnosed in pregnant women with COVID-19 than in those uninfected (17.2 and 4.0 % cases, respectively, p = 0.015), particularly in those infected in the second and third trimesters (17.6 and 18.9 %, respectively). Pregnant women with COVID-19 showed an increase in glucose levels by 1.14 times (p = 0.001), oxidized LDL by 1.24 times (p = 0.042), and apo B protein by 1.14 times (p = 0.025) in blood serum. Conclusions. Infection with COVID-19 in the second trimester of pregnancy increases the risk of GAH by 2.56 times, and in the second and third trimesters, the risk of GDM by 4.3 times. Increase of glucose, oxidized LDL, and apo B content in blood serum may have prognostic significance in the development of hypertensive disorders.

Исследование посвящено изучению особенностей потенциала «мягкой силы» интернет-мемов, ограниченных тематикой COVID-19. Представлены результаты анализа восприятия интернет-мемов молодежью 14-35 лет с учетом различий по полу. К обсуждению предлагаются тепловые карты, полученные в ходе работы с респондентами на айтрекере Tobii Pro Scerum (150 Hz), позволяющие оценить фиксацию взгляда испытуемого. Работа с группой респондентов позволила определить ключевые вербально-визуальные элементы интернет-мемов, удерживающие внимание респондентов. В исследовании сделаны выводы о реакции респондентов на стимульный материал в зависимости от возраста и пола. Определены смысловые доминанты мемов и степень их считываемости, на основании чего отмечено, что в большей степени воздействию рассматриваемых интернет-мемов подвержены молодежные группы в возрасте 14―17 и 18―24 лет, так как их восприятие характеризуется повышенным буквализмом и эмоциональностью. Различия по признаку пола менее выражены, чем различия между возрастными группами. Благодарность. Работа была выполнена при поддержке Российского фонда фундаментальных исследований в рамках гранта «Soft power-потенциал интернет-мемов: ключевые механизмы воздействия» № 21-011-32197 опн_мол.

The purpose of the present study was to evaluate the effect of DEFB1-20G>A and the DEFB1- 52G>A gene polymorphisms on the expression of DEFB1 in military-age patients with a history of communityacquired pneumonia. A survey of 160 unrelated patients of military age (18-20 years), Caucasian origin was carried out. The first group (n = 80) included the patients with COVID-19 infection complicated by mild pneumonia (n = 40) and severe pneumonia (n = 40). The second group was taken for clinical comparison (n = 80) included the patients with acute respiratory infection (ARI) of non-influenza etiology, complicated by mild pneumonia (n = 40) and severe pneumonia (n = 40). The control group consisted of 86 practically healthy men of the same age. Exclusion criteria were as follows: presence of family relations; patients with acute and/or chronic concomitant pathology. Research methods included clinical laboratory techniques (immunological testing of DEFB1 using a set of ELISA reagents Cloud-Clone Corp. (USA); genetic (polymorphism of the DEFB1-20G>A gene, DEFB1-52G>A gene) with standard primer sets of Litech-SNP (Russia); instrumental examination (computed tomography). The studies were carried out upon admission to the hospital. Statistical evaluation was carried out using the IBM SPSS Statistics Version 25.0 software package (IBM, USA). Predominance of -20A- alleles and genotypes was established -20A/A and -52A/A of the DEFB1 gene variants in the patients with development of severe pneumonia associated with COVID-19 infection. There was an increase in the DEFB1 content in the group with COVID-19 infection by 1.1 times compared with the ARI group, and a 1.5-fold increase against the control group. The changed levels of DEFВ1 associated with severity of community-acquired pneumonia were also characterized by its 1.7-fold increase in the group with a severe clinical course in presence of COVID-19 infection, and by 1.2 times in patients with ARI. The DEFB1 concentration increases significantly in the carriers of DEFB1 -20A/A and -52A/A genotypes. In patients of military age with community-acquired pneumonia, an increased concentration of DEFВ1 is registered, with highest values observed in the group with severe pneumonia due to COVID-19. Carriage of -20A/A and -52A/A genotypes of DEFB1 gene is associated with increased contents of DEFB1. Presence of -20A alleles, -20A/A, and -52A/A genotypes of the DEFB1 genes is associated with severe community-acquired pneumonia associated with COVID-19 infection in patients of military age.

The aim of this work was to study the capacity of human T cells immune for SARS-CoV-2, to produce IFNγ, a marker of T cell immunity, in response to stimulation by a peptide pool in whole blood. Eighty samples of whole blood were received from the volunteers with known medical history in 2021, and 258 volunteers were examined in September-October 2022. In this study, 2 detection techniques were used, i.e.: (1) solid-phase enzyme immunoassay to determine antibodies of class G to RBD SARS-CoV-2; (2) IGRA test to determine IFNγ produced by antigen-specific lymphocytes in response to their stimulation by viral antigen. The parameters of the IGRA test were optimized with a sample of 80 specimens from the volunteers. The threshold value of the IFNγ level was determined (4.85 pg/mL), at the diagnostic specificity of 100% (80.6-100), and diagnostic sensitivity of 92.19% (83-96.6%), 95% CI. The study was further continued with a sample of 258 volunteers. Of them, 28.7%, did not exceed the threshold level of IFNγ after stimulation, according to results of the IGRA test. Meanwhile, all volunteers exhibited class G antibodies to RBB SARS-CoV-2. There was no correlation between the levels of antibodies and the level of interferon response in the entire group. When comparing IgG antibody levels and the amplitude of IFNγ (if exceeding the baseline level) in the groups differing in the time of the last vaccination, the median values of the parameters were slightly higher for the subgroup which was revaccinated 1-2 months before the study, while a significant difference between these subgroups was revealed only when evaluating IFNγ, pg/mL (Mann–Whitney criterion, p = 0.0321). According to the results of the study, it can be assumed that all the patients in the sample who were vaccinated and had COVID-19 infection, showed a humoral immune response. However, about a third of them lacked cellular immunity to SARS-CoV-2. There was no correlation between the levels of antibodies and the level of interferon response (Spearman’s criterion). Revaccination within previous 1-2 months has been shown to promote the increased amplitude of interferon response.

Background. Research results on the immune response and cytokine profile in children with the new coronavirus infection SARS-CoV-2 are contradictory and insufficient, which necessitates the need to understand the nature of the course of the disease depending on age and severity of the infection. The importance of assessing risks and predicting the consequences of a new coronavirus infection in childhood makes the study of serum concentrations of pro-inflammatory and anti-inflammatory cytokines relevant.The aim. To study the level of pro-inflammatory and anti-inflammatory cytokines in newborns during the acute period of a new coronavirus infection to determine the characteristics of the immune response and identify prognostic criteria for the course of the infectious process.Materials and methods. The article presents the results of a study of the level of pro-inflammatory, anti-inflammatory cytokines and C-reactive protein (CRP) in newborns (n = 44) hospitalized with a confirmed new coronavirus infection of varying severity. The study was conducted during the acute period of COVID-19.Results. Cytokine concentrations in the blood serum of newborns were determined by enzyme immunoassay. In newborns in the acute period of a new coronavirus infection, regardless of the severity, there is a decrease in serum concentrations of interleukin-1β, interleukin-4, interleukin-6, interleukin-8, tumor necrosis factor α, interferon (INF) γ and CRP compared with the control group. The level of INF-α in the blood serum of newborns of both the main and control groups did not have significant differences.Conclusions. The cytokine profile in newborns with the new coronavirus infection SARS-CoV-2 may be due to inhibition of the innate immune system, which requires further research in this direction and increased pediatric attention to this category of children.

Background. The antiviral drug Remdesivir has been widely used for etiotropic treatment of COVID-19. The incidence of adverse reactions during Remdesivir therapy reaches 66.2 %, the most common one being an increase in hepatic transaminases.The aim. To develop a machine learning model for predicting the risk of drug-induced liver damage in patients with COVID-19 when prescribing Remdesivir therapy.Materials and methods. This prospective open-label observational study was conducted between November 2021 and February 2022, including 154 patients receiving Remdesivir therapy. Patients were divided into two groups: group 1 (n = 45), in which patients developed signs of liver damage during Remdesivir therapy; group 2 (n = 109) – patients without this adverse reaction. All patients underwent pharmacogenetic study and retrospective analysis of medical histories, database with the results of the conducted studies was formed, basing on which machine learning models for predicting the risk of drug-induced liver damage were trained.Results. The main prognostic factors included body mass index (relevance – 12.03 %) and carriage of AG genotype at polymorphic marker rs776746 of CYP3A5 gene (relevance – 10.04 %). Subsequently, for all obtained factors and based on Сategorical boosting a model for predicting the development of drug-induced liver damage with 57.8 % sensitivity and specificity of 80.7 % was developed.Conclusions. A risk model for the development of drug-induced liver damage during remdesivir therapy was built using machine learning. Body mass index and carriage of AG genotype at polymorphic marker rs776746 of CYP3A5 gene turned out to be key markers. To improve the accuracy of the model, an increase in the proportion of patients with adverse reactions in the training sample is required. Further studies will improve the quality of the model and integrate it into clinical practice.

The aim of the study is to apply mathematical methods to generate forecasts of the dynamics of random values of the percentage increase in the total number of infected people and the percentage increase in the total number of recovered and deceased patients. The obtained forecasts are used for retrospective forecasting of COVID-19 epidemic process dynamics in St. Petersburg and in Moscow. Materials and methods. When conducting a retrospective analysis and forecasting the dynamics of the total number of cases and the dynamics of the total number of patients who have either died or recovered, the values of percentage increases in these indicators were used. Retrospective analysis and forecasting of the dynamics of the COVID-19 epidemic process were carried out over 14-day time intervals, starting from March 25, 2020 to January 20, 2021, using the time series forecasting method proposed by the authors. Results and discussion. The retrospective two-week forecasts of the total number of cases and the number of active cases presented in the paper demonstrated a high accuracy performance, both in Moscow and St. Petersburg. The MAPE (mean absolute percentage error) for the total number of cases at the peaks of incidence, generally, did not exceed 1%. It is shown that the accuracy of the obtained retrospective forecasts of the total number of cases in St. Petersburg, built starting from May 2020, has increased significantly compared to the April forecasts. A similar conclusion can be made regarding the forecasts of the total number of cases in Moscow in April and May 2020.

Background. Many studies indicate that pregnant women are at risk for severe morbidity, adverse gestational outcomes, and mortality following SARS-CoV-2 (COVID-19) infection. Such patients have higher rates of abortion at various times, preterm delivery, preeclampsia, caesarean section, and delivery of low birth weight (LBW) newborns. Aim. To improve pregnancy and childbirth outcomes in women with COVID-19 by optimizing diagnostic and treatment interventions. Materials and methods. An open-label prospective continuous cross-sectional study enrolled 114 patients following SARS-CoV-2 infection. In 32 pregnant women of the main group with a high risk of obstetric complications, the treatment approach included endotheliotropic agent sulodexide and acetylsalicylic acid in addition to the standard of care for the underlying disease. Results. The severe course of COVID-19 in pregnant women is associated with the high rate of placental disorders (odds ratio – OR 6.1; 95% confidence interval – CI 2.6–14.9), fetal growth retardation (OR 5.6; 95% CI 1.2–30.2), preeclampsia (OR 8.5; 95% CI 3.4–22.4), premature birth (OR 14.1; 95% CI 5.8–38.4), surgical delivery (OR 8.5; 95% CI 4.1-18.1), low birth weight of newborns (OR 18.0; 95% CI 6.4–62.2), hospitalization in the neonatal intensive care unit (OR 25.4; 95% CI 6.4–67.0). Conclusion. Improving the management of pregnant women with COVID-19 by identifying a high-risk group for gestational complications, based on their early diagnosis, timely delivery, and use of acetylsalicylic acid and endotheliotropic agents to prevent venous thromboembolic complications, in addition to the standard of care, reduces the frequency of placental disorders by 2.3 times, severe preeclampsia – by 2.9 times, premature birth at 28–37 weeks – by 2 times, surgical delivery by cesarean section – by 1.6 times, delivery of low birth weight newborns – by 2.3 times, hospitalization in the intensive care unit of newborns – by 2.5 times.

Background. Viral respiratory tract infections treatment, especially during epidemic outbreak, is a main priority for pediatricians and physicians of other specialties. After the COVID-19 pandemic, a need to assess the efficacy and safety of the interferon inductor drug arose due to the changes of respiratory viruses circulation.Objective. To evaluate the effectiveness of drug within the complex therapy of viral respiratory tract infections in children aged 3 to 18 years, in comparison with standard therapy in routine outpatient practice.Materials and Methods. The study included 534 children aged 3 to 18 years diagnosed with mild to moderate viral respiratory tract infections with a disease duration of no more than 3 days at the time of enrollment in the observational program. Standard therapy was prescribed by the attending physician in accordance with current Clinical Guidelines and Treatment Standards. Additionally, Кagocel® tablets, 12 mg, were administered at the physician’s discretion, in doses of 6 or 10 tablets over a period of 4 days. Symptom dynamics, disease duration, incidence of complications, antibiotic prescriptions, recurrent viral respiratory tract infections, and viral pathogen elimination based on PCR diagnostics were assessed. Safety assessment included adverse event recording.Results. Incorporating of interferon inductor into standard therapy reduced the duration of the primary disease and accelerated symptom resolution, decreased the frequency of complications, antibiotic prescriptions, and recurrent viral respiratory tract infections. Complex therapy with an Кagocel® provided twice the effectiveness in terms of viral elimination rates compared to standard therapy without antiviral agents on days 5-8 from the start of treatment. Кagocel® demonstrated a good adverse event profile, with no AEs recorded.Conclusion. The significant efficacy of interferon inductor in the complex treatment of viral respiratory tract infections compared to standard therapy without antiviral agents in real-world practice has been demonstrated. The therapy demonstrated an excellent adverse event profile in children aged 3 to 18 years.

Aim. To study the prognostic significance of hematologic indices: neutrophils/lymphocytes (N/L), platelets/lymphocytes (P/L) and lymphocytes/C-reactive protein (L/CRP) in relation to the complicated course of new coronavirus infection (COVID-19), as well as their correlation with COVID-19 course severity indices and endothelial dysfunction marker sVCAM-1. Materials and methods. 103 patients with new coronavirus infection (COVID-19) were included in the study. Based on the data of multispiral computed tomography (CT) of the chest organs, all patients were divided into 3 groups: CT group 1 – 30 patients, CT group 2 – 62 patients and CT group 3 – 11 patients. Results. The values of N/L and P/L were significantly higher in patients of CT group 3 compared to patients of CT group 1 and CT group 2. L/CRP index, on the contrary, significantly decreased with increasing CT-degree of lung lesion. The concentration of endothelial dysfunction marker sVCAM-1 was significantly higher in patients of CT-3 and 2 groups compared to patients of CT-1 group – 272.7 [267.4; 342.6] ng/mL and 212.5 [90.3; 335.6] ng/mL vs 120.0 [75.3; 189.2] ng/mL. Significant correlations of the studied hematologic indices with clinical, laboratory and instrumental characteristics of COVID-19 severity were found. P/L and L/CRP indices were associated with sVCAM-1 concentration in blood (r=0.28 and -0.33 respectively; p0.05). The values of N/L2.53 and L/CRP≤0.043 are predictors of the development of cytokine storm in the examined patients. Conclusion. Hematologic indices N/L, P/L and L/CRP are correlated with clinical, laboratory and instrumental characteristics of COVID-19 severity, presence of endothelial dysfunction (P/L and L/CRP) and allow predicting the development of cytokine storm (N/L and L/CRP).

The aim of the study. To investigate the peculiarities of changes in hormonal and metabolic markers and their relationships with neurovegetative disorders in patients with coronary artery disease after suffering from the COVID-19 coronavirus disease (in the long-COVID period). Materials and methods. 71 patients with coronary artery disease were examined: stable angina pectoris II–III FC (age 69.0 (64.0; 76.0) years): 1 group (main) – 31 patients with coronary artery disease after suffering from the COVID-19 coronavirus disease (in the long-COVID period); Group 2 (comparison) – 40 patients with coronary artery disease who did not have a history of COVID-19. 15 practically healthy people were included in the control group. The concentration of vasopressin, ghrelin, and insulin in blood serum was estimated using immunoenzymatic analysis. The HOMA index is calculated according to the generally accepted formula. Statistical data processing was carried out in accordance with modern requirements. Results. Significant changes in hormonal and metabolic markers were found in patients with coronary artery disease in the long-COVID period in comparison with the control group and with patients without a history of COVID-19: an increase in the concentration of vasopressin by 70.23 % and 33.38 %, insulin by 52.16 % and 32.76 %, glucose level by 31.20 % and 20.00 %, HOMA index by 60.00 % and 35.77 %, reduction of active ghrelin level by 45.71 % and 49.20 % (p < 0.05) respectively. The number of patients with insulin resistance in the 1st group was significantly higher compared to the 2nd group (χ2 = 0.516, p < 0.001). Inverse correlations were established between the level of ghrelin and vasopressin (r = -0.33, p < 0.05), insulin (r = -0.25, p < 0.05) and the HOMA index (r = -0.24, p < 0.05); direct correlation between the level of vasopressin and the HOMA index (r = +0.26, p < 0.05). In addition, a wide range of reliable correlations between the level of vasopressin, ghrelin and the degree of anxiety-depressive, cognitive and autonomic disorders were found in patients with coronary artery disease in the long-COVID period. Conclusions. The obtained results confirm common mechanisms between the development of hormonal and metabolic disorders and the occurrence of anxiety-depressive, cognitive disorders, vegetative imbalance against the background of overstrain of functional adaptation processes in patients with coronary heart disease in the long-COVID period.

Aim. The purpose of the work is to analyze the biochemical indicators of liver function in relation to indicators of inflammation in patients with coronavirus disease (COVID-19) with pneumonia, taking into account the development of oxygen dependence. Material and methods. 123 patients with COVID-19 with pneumonia were examined. The diagnosis was confirmed by isolation of RNA-SARS-CoV-2 from the nasopharyngeal mucus by polymerase chain reaction. The presence of pneumonia in all patients was confirmed by X-ray or computer tomography of the chest organs. The patients were divided into groups: I group – 32 patients with a moderately severe course without oxygen dependence; II group – 91 patients with a severe course with oxygen dependence. Exclusion criteria from the research were: the presence of infection with hepatotropic viruses and the presence of previously diagnosed other chronic liver diseases. Statistical data processing was carried out in the program Statistica for Windows 13 (StatSoft Inc., No. JPZ804I382130ARCN10-J). Results. In 45.5 % of patients with COVID-19 with pneumonia at the time of hospitalization by 9.0 [7.0; 12.0] days of the disease, liver damage with the development of cytolytic syndrome was confirmed. The frequency of liver damage in patients with COVID-19 with pneumonia increased with the appearance of oxygen dependence (25.0 % vs. 52.7 %, p = 0.007). Biochemical signs of the syndrome of intrahepatic cholestasis were weakly expressed, with the appearance of oxygen dependence, they were characterized by an increase the number of patients with an elevated level of gammaglutamyltranspeptidase (59.7 % vs. 24.0 %, p = 0.002) in the absence of statistically significant changes in the median indicators activity of gammaglutamyltranspeptidase and alkaline phosphatase (p > 0.05). The relationship between liver damage and the development of oxygen dependence in patients with COVID-19 with pneumonia is confirmed by the correlation between the activity index of alanine aminotransferase (ALT) and the oxygen saturation index (r = -0.31, p < 0.05). In patients with COVID-19 with pneumonia in the dynamics after a week in presence of oxygen dependence, a higher level of activity of ALT remained (p < 0.05) and the frequency of detection of increased activity of ALT remained higher (62.6 % vs. 37.5 %, χ2 = 6.07, p = 0.01), the activity of aspartate aminotransferase is higher (p < 0.05), compared to patients with COVID-19 with pneumonia without oxygen dependence. A higher frequency of liver damage in patients with COVID-19 with pneumonia in presence of oxygen dependence is combined with more pronounced changes in acute inflammatory parameters, namely a higher level of C-reactive protein (CRP) in blood serum (p < 0.01), more frequent (p = 0.001) and more pronounced (p = 0.004) absolute lymphopenia, a higher level of absolute neutrophilia (p = 0.03) and, accordingly, a higher coefficient of N/L ratio (p = 0.0001). The oxygen saturation indicator correlates with the indicators: CRP (r = -0.37, p < 0.05), relative (r = +0.36, p < 0.05) and absolute (r = +0.23, p < 0.05) number of lymphocytes, the absolute number of neutrophils (r = -0.32, p < 0.05) and the ratio of N/L (r = -0.42, p < 0.05). Conclusions. Liver damage with the development of cytolytic syndrome was established in 45.5 % of patients with COVID-19 with pneumonia at the time of hospitalization. The dependence of the frequency of liver damage with the appearance of oxygen dependence, as well as the relationship with acute inflammatory indicators, was demonstrated.

The publication raises the issue of finding ways to reduce the level of thrombotic complications in patients with community-acquired pneumonia associated with COVID-19. Aim. To determine the effect of anticoagulant therapy on the immune and inflammatory response in patients with community-acquired pneumonia associated with coronavirus infection. Material and methods. An open, prospective, observational study was conducted in the period from January 2021 to February 2022 at the Kherson City Clinical Hospital named after Athanasius and Olga Tropin of the Kherson City Council, 143 patients with community-acquired pneumonia aged 46 to 65 years who tested positive for SARS-CoV-2 were observed. To participate in the study, patients signed a voluntary consent form. Results. Patients with community-acquired pneumonia develop an immune-inflammatory response characterized by increased levels of interleukin-6 and C-reactive protein, with significantly higher values of these biomarkers in combination with COVID-19. Combination therapy is effective in reducing the levels of markers of the immune-inflammatory response Heparin at a dose of 1000 IU/h is more effective in reducing the risk of death in patients with community-acquired pneumonia associated with coronavirus infection than 100 IU anti-Xa/kg (1 mg/kg) twice daily. Conclusions. The results of our study showed that therapy with heparin is more effective than enoxaparin in reducing interleukin-6 levels within 72 hours (by -12.93 % vs -4.75 %, respectively, p < 0.05). Multivariate regression analysis determined that changes in the levels of D-dimer, interleukin-6 and INR were independent predictors of adverse disease outcome.

The article presents a clinical case of rehabilitation of a patient with moderate cognitive and motor impairment after a COVID-associated stroke. The patient received a complex of rehabilitation measures with daily individualized cognitive training. By the end of the course of medical rehabilitation, the set goals were achieved: the patient learned to make simple decisions on her own, perform separately assigned tasks, independently attend physical therapy classes, physiotherapy, a canteen, walk around the room without the use of aids, climb to the 2nd floor without shortness of breath. The patient showed an improvement in cognitive functions: motor, dynamic and constructive praxis, object gnosis, visual-constructive skills, attention, abstract thinking and speech.

Aim. To assess the relationship between arterial stiffness and renin-angiotensin system (RAS) gene polymorphism in patients with COronaVIrus Disease 2019 (COVID-19).Material and methods: 100 patients (mean age of 58.1±11.98 years; 51% women, 49% men) were included in the cross-ectional study. This study included adult patients with laboratory-confirmed diagnosis of COVID-19 admitted to the University Hospital. All patients were evaluated for arterial stiffness using cardio-ankle vascular index (CAVI) by sphygmomanometry. Also alleles and genotypes of several polymorphic markers were identified by real-time polymerase chain reaction in human DNA preparations: rs4762 of angiotensinogen (AGT) gene, rs1799752 of angiotensin-converting enzyme type 1 gene (ACE1), rs5186 of angiotensin II type 1 receptor gene (ATP1), and rs1403543 of angiotensin II type 2 receptor gene (ATP2). The distributions of alleles and genotypes in groups with normal and elevated arterial stiffness (CAVI ≥9.5) were compared.Results. Elevated arterial stiffness (CAVI ≥9.5) was found in 29%. A significantly higher frequency of ATP1 rs5186 genotypes including the A allele, i.e., A/A+A/C versus C/C, was found in subjects with normal CAVI: 95.0% and 5.0% compared with 87.5% and 12.5% in those with CAVI ≥9.5 (χ2=3.907, p=0.049). A significantly higher frequency of genotypes involving the D allele (DD and ID) was detected in patients with increased stiffness: 95.0% compared to 81.3% in the group with normal stiffness (χ2=9.280, p

Aim: to investigate the content of eNOS in the blood serum of patients with coronavirus disease (COVID-19) with pneumonia in association with hemostatic parameters and to determine its prognostic value in assessing the risk of oxygen dependence and death. Material and methods. There were 123 patients with COVID-19 with pneumonia under observation. All patients were examined and treated in accordance with the Order of the Ministry of Health of Ukraine No. 722 dated 28.03.2020. The eNOS content in the patients’ serum was determined by enzyme-linked immunosorbent assay. Results. It was found that the content of eNOS in the blood serum of patients with COVID-19 with pneumonia at the time of hospitalization was 9.0 [7.0; 12.0] days lower (p < 0.001) than in healthy subjects. The development of oxygen dependence in patients with COVID-19 with pneumonia was accompanied by worsening of endothelial dysfunction and procoagulant changes, which was confirmed by a decrease in the content of eNOS in the blood serum (p < 0.001), an increase in the level of fibrinogen (p < 0.05) and D-dimer (p < 0.05). The threshold level of eNOS in the blood serum ≤327.09 pg/ml (AUC = 0.861, p < 0.001) was predictive of the onset of oxygen dependence. In patients with COVID-19 with pneumonia who subsequently died, at the time of hospitalization, eNOS levels were lower (p < 0.001) than in patients who recovered, which was combined with a higher level of D-dimer (p < 0.05) and its more frequent increase (p = 0.04) compared with patients who recovered. The eNOS content in the blood serum of patients with COVID-19 with pneumonia was correlated (p < 0.05) not only with the lethal outcome of the disease, but also with the formation of thrombotic complications, which occurred more often in patients with COVID-19 with pneumonia in the event of an adverse outcome (p = 0.0001). The threshold level of eNOS in the blood serum ≤201.75 pg/ml (AUC = 0.892, p < 0.001) was indicative of a high probability of death. Conclusion. The eNOS content in the blood serum of patients with COVID-19 pneumonia at the time of hospitalization is lower (p < 0.001) than in healthy individuals, and the degree of its decrease depends on the severity of the disease, the development of oxygen dependence and the subsequent outcome of this disease. Limiting levels of eNOS in the blood serum of patients with COVID-19 pneumonia, which are important for predicting the risk of developing oxygen dependence and fatal outcome of the disease, have been established.

INTRODUCTION. The high prevalence of mutations in the SARS-CoV-2 genome raises particular concerns about the resistance of the virus to current antiviral therapy, including inhibitors of the main protease, or 3C-like protease (3CLpro), and RNA-dependent RNA polymerase (RdRp).AIM. This study aimed to analyse the prevalence, spectrum, and causes of SARS-CoV-2 mutations conferring resistance to approved and pipeline RdRp and 3CLpro inhibitors on the basis of clinical, virological, and genotypic data.DISCUSSION. The authors have analysed the prevalence of SARS-CoV-2 mutations conferring resistance to antivirals (RdRp inhibitors, including remdesivir and molnupiravir, and 3CLpro inhibitors, including paxlovid) in 2021–2024. The results suggest that certain mutations existed prior to the use of these antivirals. The prevalence of resistance-conferring mutations does not exceed 0.5% of the global population. However, the results of clinical and experimental studies demonstrate the possibility of a more than 200-fold reduction in susceptibility to medicinal products and, in particular, the emergence of multidrug-resistant variants. This is especially important for immunocompromised patients. SARS-CoV-2 can persist in such patients for many months, during which spontaneous or selection-driven mutations can render antiviral therapy ineffective. This would create a risk of spreading drug-resistant variants and/or a risk of adverse outcomes for patients.CONCLUSIONS. As COVID-19 treatment coverage increases, there may be a rise in drug-resistant variants of the virus. The presented data indicate the need for genomic epidemiological surveillance, including an analysis of potential targets for medicinal products based on clinical observations. In the future, surveillance data may determine the treatment strategy and the need to develop new antivirals (RdRp and protease inhibitors) adjusted to resistant SARS-CoV-2 variants.

Information continues to accumulate about the characteristics of the course and outcomes of pregnancy and childbirth during the manifestation of the new coronavirus infection COVID-19. Most studies focus on the third trimester of gestation. Data on the impact of COVID-19 on a pregnant woman and fetus in the second trimester are scarce and contradictory. The aim of the research – to assess the characteristics of the course and outcomes of pregnancy in women with the manifestation of COVID-19 of varying severity in the second trimester of gestation. Materials and methods. 456 pregnant women with manifestations of COVID-19 of varying severity in the second trimester of gestation - the main study group. Patients of the main group, depending on the severity of COVID-19, were divided into 4 groups: with a mild course (n = 137) – group 1, with a moderate course (n = 259) – group 2, with a severe course (n = 50) – 3 group with extremely severe infection (n = 10) – group 4. 90 women in the third trimester of gestation who had no history of COVID-19 during this pregnancy – a comparison group. Results. COVID-19, which manifests itself in pregnant women in the second trimester, is statistically significantly more likely to have a mild and moderate course in the cohort of hospitalized patients (p < 0.001). Against the background of the manifestation of COVID-19 of any severity, there is a statistically significant increase in the frequency of PN compared with uninfected pregnant women (p < 0.001; p1.5 < 0.001; p2.5 < 0.001; p3.5 < 0.001; p4.5 < 0.001). Diabetes mellitus is registered statistically significantly more often in severe and extremely severe cases compared to pregnant women without COVID-19 (p = 0.001; p3.5 = 0.005; p4.5 = 0.002). During the period of manifestation, as the severity of COVID-19 increases, it is accompanied by a statistically significant increase in the frequency of premature birth (p < 0.001; p1.3 = 0.002; p1.4 < 0.001; p2.3 < 0.001; p2.4 < 0.001; p3.4 < 0.001). Induced premature births are registered statistically significantly more often in severe and extremely severe infections (p = 0.001; p1.3 = 0.005; p1.4 = 0.005). In cases of extremely severe COVID-19, cases of maternal death are recorded (2/456 – 0.4 %). Mild and moderate COVID-19 is associated with a statistically significantly higher rate of stillbirth (p = 0.001; p1.3 = 0.005; p2.3 = 0.002). During the period of convalescence after severe COVID-19, a statistically significantly higher incidence of diabetes mellitus that developed during pregnancy is recorded (p < 0.001; p1.3 = 0.001; p2.3 = 0.002; p3.5 < 0.001). Delivery is associated with a statistically significant increase in the rate of cesarean section in convalescents with mild and moderate COVID-19 compared with uninfected pregnant women (p = 0.002; p1.5 = 0.001; p2.5 < 0.001). Regardless of the severity of the infection, there is a statistically significant decrease in the weight of newborns in convalescents compared to pregnant women without COVID-19 (p < 0.001; p1.5 = 0.002; p2.5 < 0.001; p3.5 = 0.002). Conclusion. Against the backdrop of the manifestation of COVID-19 in the second trimester, the likelihood of complications of pregnancy and childbirth and adverse perinatal outcomes increases. The period of convalescence, in general, is associated with the successful completion of gestation for the mother and fetus, regardless of the severity of COVID-19 in the anamnesis.

The new coronavirus infection COVID-19, according to a number of studies, is associated with an increased risk of gestational complications and poor obstetric and perinatal outcomes. The question of the influence of gestational age at the time of manifestation of COVID-19 on the course of pregnancy and childbirth, their outcomes for the mother and fetus remains controversial. The aim of the research – to determine the characteristics of the course of pregnancy, obstetric and perinatal outcomes during the manifestation of COVID-19 of varying severity in the first trimester of gestation. Materials and methods. The study included 251 pregnant women. The main group consisted of 161 pregnant women with manifestations of COVID-19 of varying severity in the first trimester of gestation. Patients of the main group were divided into 3 groups based on the severity of COVID-19: group 1 – mild (n = 84), group 2 – moderate (n = 74), group 3 – severe infection (n = 3). The comparison group included 90 pregnant women in the third trimester of gestation without a history of COVID-19. Results. COVID-19 in the first trimester of gestation has a predominantly mild and moderate course. Against the background of manifestation, regardless of the severity of the infection, a high frequency of missed miscarriage is recorded. In moderate cases of COVID-19, both during the period of manifestation and in convalescents, the incidence of diabetes mellitus that first developed during pregnancy increases statistically significantly. Features of the course of labor during the period of convalescence have not been established. Newborns have a statistically significantly lower body weight at birth. Conclusion. The period of manifestation of COVID-19 in the first trimester of pregnancy, even with a mild infection, is associated with a high frequency of spontaneous miscarriage (statistically significantly more often in the form of a missed miscarriage). During the period of convalescence, pregnancy is characterized by favorable obstetric and perinatal outcomes.

Background. COVID-19 negatively impacts pregnancy progression and outcomes. However, data regarding pregnancy complications related to prostaglandin activity during COVID-19 remain insufficient.The aim. To assess markers of metabolic processes related to prostaglandin metabolism in the blood of pregnant women depending on the severity of COVID-19 and to explore associations with the development of pregnancy complications.Methods. The study included 109 pregnant women in their third trimester (28–30 weeks), 36 of whom had mild COVID-19, 38 had moderate COVID-19, and 35 were not infected with SARS-CoV-2. The concentration of prostaglandins E2 and F2α, phospholipase A2 (PLA2), cyclooxygenase 2 (COX2), and arachidonic acid (AA) were measured in the blood using enzyme-linked immunosorbent assays and gasliquid chromatography for AA.Results. Comparative analysis showed that pregnant women with moderate COVID-19 had significantly higher levels of AA, COX2, PLA2, prostaglandins E2 and F2α (p < 0.0001) compared to those with mild disease. These women also experienced more frequent complications, such as chronic placental insufficiency, preterm labor, and premature rupture of membranes. Regression analysis revealed associations between chronic placental insufficiency and prostaglandin E2 levels (p < 0.0001), preterm labor, AA (p = 0.001) and COX2 (p = 0.001); premature rupture of membranes and PLA2 (p = 0.025), COX2 (p < 0.001), AA (p < 0.001).Conclusion. Moderate COVID-19 during the third trimester of pregnancy is associated with increased levels of AA, COX2, PLA2, and prostaglandins E2 and F2α in the blood. The most significant factors increasing the risk of pregnancy complications in women with moderate COVID-19 were elevated levels of AA, COX2, and prostaglandin E2 in the blood.

Background. T cell immunity is known to play a central role in controlling SARSCoV- 2 (severe acute respiratory syndrome-related coronavirus 2) infection, so it is critical to understand its role in recovery from COVID-19 (coronavirus disease 2019), especially in the unfavorable conditions of the North.The aim. To assess the immune status of women after COVID-19 living in the subarctic region of the Russian Federation.Materials and methods. We examined a total of 50 women aged 36–46 years, including 38 vaccinated women 6 and 12 months after recovery from COVID-19 and 12 women (control group) who had not had COVID-19 and had not been vaccinated (Arkhangelsk region). We studied leukocyte count, leukogram and lymphocyte phenotypes (CD5+, CD8+, CD10+, CD16+, CD95+).Results. The contribution of monocytes to the formation of the adaptive immune response among female residents of the subarctic region decreases in those who have had mild COVID-19 and increases in those who have had moderate COVID-19. It was found that the imbalance in the formation of the immune response after COVID-19 is formed due to innate immunity (CD16+, neutrophils (r = 0.89; p < 0.001)), affects the adaptive immunity and depends on the severity of the disease and the time since recovery. The most significant contribution to the formation of the adaptive immune response was established due to cellmediated cytotoxicity (CD8+, CD16+) and the activity of apoptotic processes (CD95+) both after 6 and 12 months and does not depend on the severity of the COVID-19. The adaptive immune response formed 6 months after COVID-19 with a high level of cell-mediated cytotoxicity and activity of apoptotic processes prevailing over lymphoproliferation persists after 12 months, which indicates a tense state of immune homeostasis.Conclusion. In the examined women who had recovered from COVID-19, cellmediated cytotoxicity (CD8+, CD16+) is associated with the activation of the monocyte system, has a prolonged effect of up to 12 months and depends on the severity of the previous COVID-19 in 66.7–90 % of cases.

As is known, the issues of pathogenesis, diagnosis and treatment of the new coronavirus infection COVID-19 are the most priority areas of scientific research in the modern clinic of internal diseases. The rate of emergence of new scientific data in the leading libraries PubMed, Medline, Cochrane Library and eLibrary, which can potentially be important in the correction of ongoing therapy for infection and its complications, is extremely high. In turn, this dictates the need for a comprehensive discussion of the results of newly published studies. These issues include clinical and neurological manifestations of COVID-19 and other coronavirus infections. The exact mechanism by which the SARS-CoV-2 virus enters the structures of the central nervous system is unknown. Thus, two pathways for the penetration of the COVID-19 pathogen are most actively discussed: the hematogenous pathway (through the systemic circulation into the vessels of the brain with a low linear blood flow velocity, which allows the virus to adhere to the surface of the endothelium and penetrate into the nervous tissue through damage to the latter) and the contact pathway (through the cribriform plate and the olfactory bulb). It should also be noted that a number of experimental works clearly demonstrate the pathogenic effect of other members of the Coronaviridae family on the neurons of the respiratory and vasomotor centers. The review presents an analysis of current literature data on the study of clinical and neurological manifestations of COVID-19 and other coronavirus infections. It is important to emphasize that patients with a severe course of COVID-19 deserve special attention, requiring observation in the intensive care unit in order to prevent the development of fatal neurological complications.

Aim. Assessing the effectiveness of new baselines and intensity thresholds of epidemics based on rates of incidence and hospitalization with a diagnosis of “influenza” to clarify the timing of epidemics and their spread throughout the Russian Federation against the backdrop of the COVID-19 pandemic (from 2021 to 2024). Materials and methods. At the A.A. Smorodintsev Influenza Research Institute, the software was reformed taking into account the need to solve the tasks set during the COVID-19 pandemic. Due to changes in influenza surveillance in relation to the diagnosis of “influenza”, and hence the increase in the registration of influenza cases, the baseline and threshold of epidemics were adjusted for the influenza incidence and hospitalization rates in the surveyed cities in total (61) and for each Federal districts (over the entire population and by age groups) for 3 epidemics against the background of COVID-19 pandemic (2021–2022, 2022–2023, and 2023–2024). Results. A comparison of baselines calculated over the previous 6 seasons based on the incidence and hospitalization rates of mostly clinically diagnosed influenza and new baseline levels of incidence and hospitalization rates of mostly laboratory-confirmed influenza during the pandemic showed minor changes in the indicators of baseline incidence and hospitalization rates while epidemic thresholds for these indicators increased. Conclusion. Against the backdrop of the COVID-19 pandemic during the 2020–2021 season, there was no influenza epidemic. In 2021–2022, the A(H3N2) epidemic was of low intensity in terms of incidence, hospitalization rates and low mortality (2 cases). In 2022–2023, the influenza A(H1N1)pdm09 and B epidemic was of moderate intensity in terms of incidence, with a high frequency of hospitalizations and mortality (120 cases). Influenza A(H3N2) and B epidemic in 2023–2024 was of a “very high” level in terms of the influenza incidence, but average in terms of the frequency of hospitalizations and mortality (41 cases), with higher incidence rate compared to the previous epidemic (0.28% and 0.19% of the total population), including persons over 15 years of age (0.19% and 0.12%).

In the spring 2022, the number of cases of severe acute hepatitis of unknown etiology was unusual increased in Europe. As an immediate response, the World health organization recommended active efforts to identify such cases at the international level. For monitoring of acute hepatitis in Moscow, patients with suspected liver disease were sent to Infectious Diseases Clinical Hospital No. 1. The goal: study of the structure of diseases occurring with liver damage in children hospitalized in 2022. Materials and methods: analysis of medical records of children hospitalized with a diagnosis of hepatitis from May 1 to December 31, 2022. Еpidemiological data (age, gender, parenteral manipulations, contacts with patients, travel abroad), clinical (fever, jaundice, etc.), laboratory parameters were assessed. Results: A total of 164 completed cases of hepatitis in children aged 5 months to 17 years were analyzed. 36 children met the criteria for probable severe acute hepatitis of unknown etiology. Age median was 7 years [2.25;11]. Girls made up more than half (21 (58.3%). Non-infectious genesis was established in 15 (41.6%). The infectious disease was verified in 11 (30.5%), of which adenoviral infection was detected in 2 children. In 9 (25%) children the etiology of hepatitis was not established. Conclusion. Various infectious and non-infectious diseases among hospitalized children lead to a significant increase in liver transaminases. Most acute hepatitis with unspecified etiology proceeded as an acute infectious disease and ended in recovery. The role of adenoviruses in the development of severe hepatitis in children was not confirmed in our study.

The coronavirus infection is a pressing issue in modern healthcare, yet the characteristics of the SARS-CoV-2 infection course in children with comorbidities remain insufficiently studied. The aim of this study was to evaluate the clinical form, severity, and duration of SARS-CoV-2 virus shedding in pediatric patients with somatic diseases, depending on the comorbid pathology. Materials and Methods. A comprehensive single-center retrospective study was conducted, analyzing 314 medical records of patients hospitalized in the infectious diseases department of the Russian Children’s Clinical Hospital in Moscow over 11 months in 2022. The inclusion criterion was the presence of a laboratory-confirmed COVID-19 diagnosis. Results. Children with comorbidities were found to be predisposed to a more severe course of SARS-CoV-2 infection compared to the pediatric population in general. Children with hematological diseases were at the highest risk of adverse outcomes from COVID-19. Patients with oncological and hematological diseases and primary immunodeficiencies shed the SARS-CoV-2 virus significantly longer than patients with other somatic pathologies. The duration of SARS-CoV-2 RNA detection in patients with severe COVID-19 was significantly longer, which also correlated with the severity of the underlying somatic disease. Conclusion. Children with comorbidities are at risk for a more severe and prolonged course of SARS-CoV-2 infection.

To date, the pathogenesis of COVID-19 associated multisystem inflammatory syndrome (MIS-C) remains unclear. Despite this, it becomes obvious that the pathogenesis of MIS-C is directly related to a certain immune dysregulation, however, a clear understanding of the mechanisms of this dysregulation has not yet been formulated. In order to identify the cytokine profile in patients with MIS-C, spontaneous and stimulated production of certain cytokines in cell culture was identified. Materials and methods. The study was conducted in the following study groups: group 1 — patients with MIS-C (n = 52); group 2 (comparison group) — patients with COVID-19 associated pneumonia (n = 15); group 3 (control group) — conditionally healthy patients (n = 23). The following stimulating agents were used: S58 — recombinant antigen Spike_SARS-Cov-2; NP is a recombinant NP antigen of the coronavirus SARS-CoV-2 and a standard mitogen. Results. Тhe absence of the initially expected hyperproduction of the main pro-inflammatory cytokines (IL-6, IL-8, TNF-α, etc.) was recorded. Statistically significant developments were recorded between patients of the study groups in the spontaneous production of MCP-1, in particular, the indicated indicator was 40010.82 (19698.1; 64812.1); 643.7 (214.6; 1695.4) and 622.7 (214.6; 1068.1), respectively. The indicated spontaneous hyperproduction of MCP-1 in patients with MIS-C allows us to consider as a probable completely new theory of the pathogenesis of MIS-C associated with dysregulation of the type 2 immune response. The presence of statistically significant differences, primarily in the spontaneous production of this cytokine, can apparently be explained by the presence of genetically determined determinants associated with subsequent dysfunction of the Th2 helper immune response, a potential trigger for which is a previous COVID-19 infection. Thus, further study of the immunopathogenesis of COVID-19 associated MIS-C is required.

An increase in the frequency of patients with arterial hypertension (AH) seeking medical care and its more severe course after a novel coronavirus infection (NCI), COVID-19, determines the need to study possible pathogenetic mechanisms of disease progression. Aim of the study was to investigate some features of lipid metabolism and changes in hemostasis in patients with AH after NCI COVID-19. Material and methods. An analysis of the most informative indicators of lipid metabolism and hemostasis was carried out in 104 patients with AH underwent (more than 2 months ago) NCI, in comparison with 117 patients with AH, with no history of COVID-19. The study included men and women aged from 30 to 75 years. Determination of the concentration of lipids in blood serum was carried out using the photometric method on a biochemical analyzer AU 480 (Beckman Coulter, США). Hemostatic parameters were determined by the chromogenic method using an automatic hemostasis analyzer Technology Solution 190 (USA). Results and discussion. It was found that patients with AH underwent NCI had significantly higher serum levels of total cholesterol, LDL cho- lesterol, triglycerides, D-dimers, platelets and lower activated partial thromboplastin and thrombin time compared with patients without COVID-19. Conclusions. The data obtained indicate a tendency to atherogenic changes in the blood lipid profile and increased coagulation processes in patients with AH in the long-term period (more than 2 months) after suffering a NCI COVID-19.

The aim of the present study was to perform a comparative quantitative analysis of natural neurotropic autoantibodies (Nabs) in blood serum of patients with COVID-19 associated ischemic strokes (IS) in dynamics of disease. A total of 150 consecutive patients with acute primary IS were included, being divided in two groups: 100 patients with IS on the background of COVID-19 pneumonia (main group No. 1) and 50 patients with IS without COVID-19 symptoms and positive viral test (comparison group No. 2). The stroke severity and consciousness were measured by NIHSS and Glasgow coma scale. In blood serum of patients (n = 110), we have studied the levels of IgG Nabs to NF-200, GFAP, S100β, MBP, receptors to dopamine, serotonin, choline, glutamate, GABA by means of ELISA technique. The blood samples for analyses were taken at the 5th, 14th and 28th days of disease. In group 1 (n = 80), the Nabs levels have been increased as follows: antibodies to NF-200 (132.9±4.1 CU), by 1.09 and 1.8 times; for GFAP (118.9±3.9 CU), by 1.4 and 2 times; S100β antibodies (129.5±10.2 CU), by 1.05 and 1.6 times; MBP antibodies (97.3±4.5 CU) were 1.14 and 1.6 times higher; antibodies to dopamine receptors (77.9±4.4 CU) in 1.2 and 1.6 times; to serotonin receptors (81.96±3.25 CU) in 1.2 and 1.4 times; choline receptor antibodies (61.42±3.6 CU) were increased 1.4- and 1.8-fold; to glutamate (85.28±4.25 CU) by 1.19 and 1.4 times; to GABA (82.4±5.2 CU) the increase was 1.5- and 1.8-fold, respectively, when compared with group 2 and controls. The time-dependent monitoring of Nabs level in patients with COVID-19 associated ischemic stroke showed the highest increase in Nabs to the S-100, NF-200 and MBP proteins at the day +28 following the brain stroke. In patients with COVID-19 associated IS, more enhanced production of serum autoantibodies to neuroproteins and neurotransmitter receptors was detected, which accompanied a worse course of IS and can be considered as a predictor of unfavorable outcome of disease.

Diseases of the respiratory system are among the most common among the population of different age categories. Sound, as a physical phenomenon, is the propagation of longitudinal elastic waves in a medium, for example, in the air. Waves with frequencies below 16 Hz are called infrasound, and above 20,000 Hz are called ultrasound, and these waves cannot be perceived by the human ear. That is why the study of acoustic signals is extremely important for the diagnosis and monitoring of respiratory diseases. The aim of this article is to investigate the features of the use of acoustic diagnostic methods in pediatric practice through the analysis of contemporary literature over the past five years, sourced from Scopus and Web of Science databases, as well as conducting original clinical research. Results. Acoustic diagnostic methods in pediatrics have great potential due to their non-invasiveness and lack of radiation exposure. Literary sources indicate the high efficiency of these methods in detecting pathologies of the respiratory system in children, especially in the early stages of diseases. Our research with the acoustic monitoring device "Trembita-Corona" confirmed the ability to accurately determine the affected areas of the lungs with the help of highly sensitive acoustic sensors. The primary focus is paid to the comparative evaluation of the diagnostic efficacy, safety, and potential for using these methods in children of different age groups. It has been proven that acoustic methods allow the identification of pathological changes even in hard-to-reach extracostal areas. The effectiveness of the acoustic monitoring device "Trembita-Corona" developed and implemented in clinical practice is confirmed by the possibility of mathematical data processing, which significantly increases the accuracy of diagnosis, excluding the human factor. The use of acoustic methods in pediatrics opens up new opportunities for early detection and monitoring of diseases of the respiratory system. Conclusions. The implementation of acoustic methods into clinical practice is a promising direction that deserves further research and development. The conducted experimental studies demonstrated the ability of the "Trembita-Corona" device to accurately diagnose and localize lung lesions in community-acquired pneumonia, confirming the effectiveness of the developed methods and algorithms. No conflict of interests was declared by the authors.

Геморагічний васкуліт (пурпура Геноха-Шенлейна) є поширеним захворюванням. Йому часто передує бактерійна або вірусна інфекція верхніх дихальних шляхів. Мета - дослідити особливості перебігу та лікування геморагічного васкуліту в дитини після перенесеного COVID-19 на прикладі клінічного випадку. Наведено клінічний випадок гострого геморагічного васкуліту в 14-річного хлопчика. Дитину госпіталізовано зі скаргами на підвищення температури тіла до високих цифр, появу висипань на нижніх кінцівках, сідницях, біль і припухлість у колінних суглобах. З анамнезу життя відомо, що за 2 тижні до появи цього геморагічного синдрому переніс COVID-19. Захворювання розпочалося гостро з підвищення температури тіла до 40,1°С. Проведено детальний аналіз, пов’язаний із васкулітом/капіляритом. Під час об’єктивного обстеження виділено клінічні синдроми: інтоксикаційний, геморагічний, суглобовий. Проведено обстеження: загальний аналіз крові, загальний аналіз сечі, біохімічні аналізи. Призначено підтримувальну терапію, яка передбачала достатню гідратацію, відновлення й збереження електролітного балансу. З метою контролю болю призначено прості анальгетики (парацетамол дозою 15 мг/кг кожні 6 год перорально). Проведено диференційну діагностику з менінгококовою інфекцією, ювенільним ідіопатичним артритом, тромбоцитопенією. Наведено алгоритм діагностики геморагічного васкуліту. Обґрунтовано необхідність настороженості щодо розвитку геморагічного васкуліту в дітей, які перенесли COVID-19. Дослідження виконано відповідно до Гельсінської декларації. На проведення досліджень отримано інформовану згоду батьків дитини. Автори заявляють про відсутність конфлікту інтересів.

Introduction. The deregulated excessive pro-inflammatory cytokine secretion has a detrimental impact on the evolution of COVID-19, aggregating tissue impairment, organ failure, and increasing the risk for death. Several studies have demonstrated the beneficial effect of Tocilizumab (TCZ) in reducing hyperimmune response in severe forms of COVID-19. Materials and methods. This study is a retrospective cohort consisting of a sample of 66 patients hospitalized with COVID-19. The 1-st group consists of 33 patients treated with TCZ 200 mg IV once, and the 2-nd group – of 33 patients treated with TCZ 400 mg IV once. Results. The average age of the patients included in the study was 58,22±1,38 years. A decision regarding TCZ administration was made on average on the 11,34±0,31 day of the disease when the beginning of Cytokine Storm was suspected in the patients already on dexamethasone treatment. The dose of TCZ had significance on the duration of patients' disabilities, duration of oxygen therapy, and duration of hospitalization, with better results for TCZ 400 mg vs. TCZ 200 mg. However, we cannot prove that the dose of TCZ influences the percentage of patients transferred to the ICU for invasive or non-invasive ventilation. Conclusion. The 200 mg fixed dose of TCZ can be a life-saving option for severely ill patients with COVID-19 in the context of IL-6 inhibitor supply shortages.

Introduction: While some patients recovered, others died across the world thereby losing their loved ones. The objective of the current study is to determine statistical differences in means of the COVID-19 infected population (laboratory confirmed), discharged cases(recovered) and deaths resulting from the COVID-19 pandemic in Rivers State, Nigeria. Material and Methods: In this study, extraction of the infected population (laboratory confirmed), discharged cases, and deaths from COVID-19 was carried out from data obtained from the Nigeria Centre for Disease Control which covered 572 days (25th March 2020 - 17th October 2021). The test for the significance of means among the variables was done using a one-way Analysis of Variance (ANOVA) followed by the Tukey HSD test. The two variables whose means do not significantly differ were tested for strength of relationship and dependence using correlation analysis and cubic polynomial function respectively. Results: Results showed that there is a statistically significant difference between the infected population, discharged cases, and deaths from COVID-19 as obtained from one-way ANOVA (F(2, 1710) = 121.958, p = 0.000). Use of the Tukey HSD test indicated that the means of infected population and discharged cases do not differ from each other (p>0.01); however, mean deaths from COVID-19 significantly differ from others at 99% confidence intervals (p

Introduction. Contemporary researchers have suggested and demonstrated the hypothesis that the elevated level of D-dimers, which is a valuable marker of coagulation and fibrinolysis activation, can predict the severity of COVID-19, pulmonary complications, and thromboembolic events before they occur. Material and methods. The bibliographic resources were analyzed and selected from databases such as PubMed, Hinari, SpringerLink, and Google Search using keywords such as “COVID-19,” “SARS-CoV-2,” “coronavirus,” “D-dimers,” “biomarkers,” and “severity prediction,” which were used in various combinations to maximize search efficiency. Therefore, the manuscript contains 51 representative articles for this synthesis article. Results. The D-dimer levels are significantly higher in patients with severe forms of COVID-19 compared to those with non-severe forms, in patients with acute respiratory distress syndrome compared to those without acute respiratory distress syndrome, and in deceased patients compared to those who have survived. D-dimers positively correlate with the degree of severity and the increased risk of progression to severe disease, inversely proportional to the survival rate. They can predict prognosis, determine therapeutic strategies, prevent complications, positively influence the disease’s course, and monitor the prognosis. Conclusions. D-dimers should be used as a pre-radiographic screening tool as early as possible after admission and as an indicator for risk stratification of venous thromboembolism in hospitalized patients with COVID-19. Based on the increase in D-dimer levels, adjusting therapeutic doses of anticoagulants is more beneficial for patients compared to administering prophylactic doses.

The aim of the work was to evaluate the ability of monoclonal antibodies to inhibit the interaction of the receptor binding domain (RBD) in S protein of SARS-CoV-2 virus variants, Wuhan-Hu-1 and BQ 1.1, with the angiotensin-converting receptor 2 (ACE2). Materials and methods. In this study, recombinant RBDs of Wuhan-Hu-1 and BQ 1.1 variants were used as antigens. For mouse monoclonal antibody (mMCA) production, hybridomas were cultured in vivo in BALB/c mice. mMCAs were isolated from ascitic fluid by ammonium sulfate treatment followed by purification through column affinity chromatography with Protein G Sepharose sorbent. The specific activity of mMCAs was assessed by immunoblot with recombinant RBD of Wuhan-Hu-1 variant. To identify the most promising mMCA, the neutralizing activity of mMCA was evaluated by enzyme-linked immunosorbent assay (ELISA) via immobilizing RBD on the surface of a microplate and using ACE2 in the form of horseradish peroxidase conjugate. Recombinant antigens were produced in ExpiCHO-S cell line (Gibco, USA). Results and discussion. Three mMCAs have been described as a result of the study: 5C3, 3F11, 1E6. All antibodies belong to immunoglobulins of subclass G and specifically interact with the RBD in S protein of SARS-CoV-2 virus. The most effective inhibition of the interaction between ACE2 and the RBD of BQ 1.1 strain was observed for murine MCA 3F11 (65 %), while the interaction with the RBD of Wuhan-Hu-1 strain was inhibited by mMCA 5C3 (91 %). The identified characteristics allow for considering the antibodies as potential candidates for the development of antibody-based therapeutics, thus expanding the possibilities of therapy for SARS-CoV-2 virus infection.

Aim – to analyze the current literature on the role of single nucleotide polymorphism (SNP) of human genes in shaping the clinical course of the new coronavirus disease (COVID-19). Results. Based on the results of the analysis and synthesis of the current literature on the role of SNP in shaping the clinical course and outcome of COVID-19, the clinical and prognostic significance of SNP of genes encoding receptors responsible for the penetration of SARS-CoV-2 into target cells has been demonstrated. The presence of the D-allele of the ACE gene (DD and ID genotypes) is associated with the highest risk of severe COVID-19, which makes it possible to offer it as an informative prognostic marker of COVID-19 severity. SNP of the TMPRSS2 co-receptor gene, known as the androgen responsive gene, at certain loci is prognostically important, as it leads to an increase in TMPRSS2 expression in men, which promotes virus fusion with the target cell membrane and has an unfavorable effect on the course of COVID-19 in men. The data accumulated in the current literature on the clinical and prognostic value of SNP host genes encoding the immune response has also been analyzed. The role of HLA SNP genes, genes encoding innate immunity factors (TLR), as well as genes encoding pro-inflammatory cytokines (IL-6, TNF-α, etc.) and acute-phase inflammatory components (CRP) in the development of severe COVID-19 and the risk of death has been demonstrated. Attention has been paid to the determined role of SNP in the ACE gene in the development of pulmonary embolism in patients with severe COVID-19. The article has analyzed publications on the SNP role of host genes in the development of clinical events that are currently interpreted as long COVID. The prognostic role of the IL-10 gene SNP and its receptor gene in the formation of long-term consequences of the new coronavirus infection has been demonstrated. Conclusions. SNP of host genes encoding receptors responsible for the entry of SARS-CoV-2 into target cells and SNP of genes encoding immune response have some prognostic value in assessing the risk of severe course and adverse effects of COVID-19. The accumulation of data on genetic risk factors for adverse outcomes of the new coronavirus disease will allow us to enhance the understanding of this infection pathogenesis, improve patient stratification and individualize therapeutic interventions.

A well-known and dangerous complication of COVID-19 infection is the development of hypercoagulation, which leads to thrombosis of various localization. Therefore, the problem of anticoagulant therapy was widely discussed during the first months of the pandemic and continues to be relevant. At the same time, concomitant cardiac pathology is associated with a more severe course of COVID-19 and higher risks of complications and mortality. Therefore, patients who underwent cardiac surgery require special attention. Individuals with prosthetic metal heart valves must constantly receive anticoagulant therapy, however, the literature describes cases of intracardiac thrombotic complications despite anticoagulation during COVID-19 infection. Currently, there are no randomized studies on this issue, and only individual clinical cases provide this information. The aim of the work was to describe a clinical case of thrombosis at the left ventricular apex during COVID-19 infection in a patient with a prosthetic aortic valve who received adequate warfarin therapy and to compare the tactics of patient management and therapeutic outcomes with other clinical cases. Materials and methods. The patient was followed-up after aortic valve replacement for 2 years. During the visits, a general clinical examination, laboratory examinations – clinical blood test, blood glucose, urea, creatinine, bilirubin, INR, NT-proBNP, echocardiography were performed. Results. The patient with a congenital heart defect, a condition after aortic valve replacement, mitral and tricuspid valve annuloplasty (15.03.2022) due to bicuspid aortic valve, combined aortic defect with predominance of stage III-IV regurgitation; stage III secondary arterial hypertension; chronic heart failure IIA, functional class III, stage C, reduced systolic left ventricular function; a two-chamber pacemaker due to complete AV blockade; paroxysmal atrial flutter presented to a cardiologist with worsening shortness of breath and weakness one month after a moderate COVID-19 infection. The patient received bisoprolol 5 mg, amiodarone 200 mg, spironolactone 50 mg, perindopril 8 mg, warfarin 5 mg, INR was carefully controlled, at presentation – 3.7. Echocardiography revealed a left ventricular apex thrombus, a decrease in left ventricular ejection fraction (LVEF) from 46 % to 38 %. Aspirin 75 mg/day, torasemide 10 mg/day, dapagliflozin 10 mg/day, and metabolic therapy were added to the treatment. After 1 month, the patient’s condition improved, no thrombus was detected in the left ventricular cavity, LVEF increased to 46 %. Conclusions. This case demonstrates the problem of careful cardiovascular system state monitoring in patients with prosthetic valves during and after COVID-19, since symptoms of heart cavity or valve thrombosis, worsening heart failure can be mistakenly considered as signs of a viral infection or respiratory failure.

This article presents a literature review on visual impairments in COVID-19 and post-COVID syndrome and their possible pathogenesis. The data on possible cellular targets of SARS-CoV-2 in various damaged eye structures are discussed. The proposed approaches to the treatment of eye disorders in COVID-19 are reviewed. The main attention is given to the recently discovered family of cation channels — the channels with a transient receptor potential, or TRP channels, as possible targets of SARS-CoV-2 action on eye cells. The structure and properties of TRP channels, in particular their ability to act as receptors for temperature, pain and inflammation, and to participate in phototransduction, are examined. TRP channels are shown to be present in the anterior and posterior segments of the eye. The relationships are explored between TRP subfamilies, in particular TRPV1 channels, and various pathologies, such as dry eye syndrome, glaucoma, eye trauma, retinopathy, etc. Evidence is provided for a direct involvement of TRP channels in the pathogenesis of pulmonary pathology in COVID-19, and their role in the pathogenesis of many other diseases, including neuropathic and inflammatory pain, stroke, migraine, neurodegenerative disorders. The currently known pharmacological approaches targeting TRP channels are discussed. The paper highlights the importance of closely monitoring TRP channels activity, particularly TRPV1 ones, in assessing various COVID-19 manifestations, including eye infections.

INTRODUCTION. The risk of liver damage correlates with the severity of COVID-19. However, a growing number of studies have shown an association between liver function impairment and combinations of medicinal products used to treat COVID-19.AIM. The study aimed to analyse the annual consumption of medicinal products associated with a high risk of drug-induced liver injury (DILI) used as part of combination therapy in COVID-19 patients and to review a number of medication administration records in order to develop measures to prevent DILI.MATERIALS AND METHODS. The study used the ATC/DDD methodology to study consumption data for 2020, 2021, and 2022 and analysed a sample of 1250 inpatient medical records and medication administration records of COVID-19 patients treated in a Volgograd region hospital converted into a COVID-19 care centre. For genetically engineered biologicals and cyclophosphamide, which were lacking DDDs, the authors calculated the volume of consumption using the average dose per treatment course. The authors identified medicines capable of causing clinically apparent liver damage (according to the LiverTox database and Russian clinical practice guidelines) and/or elevated liver enzymes in ≥1% of patients (according to safety reports).RESULTS. The study found that 28% of the medicinal products used in combination for inpatient treatment of COVID-19 were associated with a high risk of DILI. In 2020, 2021, and 2022, the total consumption of medicinal products associated with a high risk of DILI was 342.3, 425.3, and 402.3 DDDs per 100 bed days, and the total consumption of genetically engineered biologicals (administered as a single dose) and cyclophosphamide was 3.5, 16.9, and 29.7 average course doses per 100 patients, respectively. According to the selective analysis of medical records, 19.8% (247/1250) reported concomitant use of 5 or more medicinal products associated with a high risk of DILI, which increased the risk of adverse drug interactions leading to DILI. In 2022, the most prescribed medicinal products with a high risk of DILI were omeprazole (188.7 DDDs per 100 bed days), non-steroidal anti-inflammatory drugs and paracetamol (54.4 DDDs per 100 bed days), atorvastatin (46.2 DDDs per 100 bed days), levofloxacin (26.4 DDDs per 100 bed days), ceftriaxone (20.5 DDDs per 100 bed days), favipiravir (17.3 DDDs per 100 bed days), and genetically engineered biologicals (24.0 DDDs per 100 bed days).CONCLUSIONS. To reduce the risk of DILI in COVID-19 patients admitted to infectious disease units, including the risk of DILI due to drug interactions, it is necessary to limit the use of hepatotoxic antibacterial agents, proton-pump inhibitors, and non-steroidal anti-inflammatory drugs, or consider alternative medicinal products with a lower risk of hepatotoxicity.

This article discusses the problem of underuse, low availability of modern imaging techniques such as magnetic resonance imaging of the heart (MRI). This technique is characterized by high accuracy and uniqueness in the diagnosis of myocardial lesions of various genesis. The widespread introduction of this technique in emergency cardiology departments can improve the accuracy of diagnosis and the effectiveness of patient therapy. Despite the high costs of implementation and current use, modern diagnostic methods can save healthcare resources by reducing hospital stays and improving treatment outcomes.

AIM OF THE STUDY. Was to improve the outcomes of treatment of patients with COVID-19-related acute abdominal pathology by developing and implementing an algorithm for the diagnosis and treatment of those patients.MATERIAL AND METHODS. The study involved 200 patients who were randomized into two groups. This research was retrospective, based on the analysis of the medical histories of patients hospitalized with clinical manifestations of acute abdominal pathology that developed against the background of COVID-19. All medical histories in emergency departments and centers of the Republic of Uzbekistan were analyzed in the period from the beginning of the declaration of the pandemic (March 2020) to July 2022 inclusive.RESULTS. In the context of an infectious disease pandemic (COVID–19 as an example), it is very important to develop an algorithm for managing patients with acute surgical pathology. This algorithm should include a diagnostic component with the purpose of timely diagnosis of acute surgical pathology and hospitalization in the surgical department. The next step is to identify patients with a high risk of perioperative complications and adverse outcomes. The final component of the algorithm is the correction of possible risk factors for adverse outcomes.CONCLUSION. The duration of hospitalization of patients who underwent surgery for acute abdominal pathology was significantly longer during the pandemic compared to that of in the post-pandemic period (10.35±7.01 vs. 5.83±3.85 days, p

The article presents a clinical case of development of mural infective endocarditis (IE) with formation of vegetations in the region of the upper third of the interventricular septum in patient A., 51 years old, with uncorrected tetralogy of Fallot. The patient was admitted with complaints of increased heart rate, interruptions in the heart work, feet swelling, shins up to the upper third, dyspnea at rest, general weakness, fever up to 39 оC, sweating, headache. During transthoracic echocardiography on the upper third of the interventricular septum (IVS) from the side of the RV, an additional echo-positive linear mobile formation 0.9 cm long is visualized, similar to the chords of the tricuspid valve. Thus, based on the identification of 1 major Duke criterion (imaging criterion — the presence of parietal vegetation) and 3 minor criteria (predisposing factors — congenital heart disease of the blue type; fever >38 оC; positive blood culture not meeting the requirements for the major criterion), laboratory and instrumental diagnostic data and anamnesis, the following diagnosis was established: "Secondary infective endocarditis with damage to the upper third of the interventricular septum". Taking into account the sensitivity of the identified microflora, polymyxin and moxifloxacin were prescribed. During therapy, a dry cough and dry wheezing in the projection of the middle lobe on the right appeared. To exclude septic embologenic pneumonia, computed tomography of the chest organs was performed, on which no focal/infiltrative changes were detected. However, a shunt connecting the brachiocephalic trunk with the right pulmonary artery was visualized, which may explain the cause of compensation of hypoxemia that arose due to pathological hemodynamics as a result of high pulmonary stenosis. Given the incomplete effectiveness of therapy, as well as the sensitivity of the infectious agents isolated, a decision was made to change antibacterial therapy to vancomycin in combination with imipenem. Conservative treatment methods allowed not only to compensate for the existing clinical symptoms, but also to achieve reference values of laboratory parameters, despite the impossibility of surgical intervention.

Laboratory data, especially a general blood test, play an important role in the treatment of infectious diseases, including COVID-19. However, in patients with coronary heart disease (CHD) and COVID-19, a general blood test is rarely analyzed and is insufficient to fully assess an impact of the new coronavirus infection on patients with cardiac diseases. The aim of the study was to analyze a COVID-19 effect on hemogram parameters in the early recovery period of patients with coronary heart disease. The study was performed at the Kursk City Clinical Hospital for Emergency Medical Care in the years 2021–2022, which involved 58 mature-aged patients (45–59 years old) suffering from coronary heart disease who had a new coronavirus infection and 62 elderly patients suffering from coronary heart disease alone. Morning blood sampling was carried out from the forearm superficial veins into Vacutainer test tubes added with a coagulation activator. In elderly patients, 3–4 weeks after recovery, significant changes in red blood parameters persisted — a decline in the level of peripheral blood erythrocytes, hemoglobin and hematocrit. Elderly patients with coronary heart disease comorbid with a moderate new coronavirus infection, 3–4 weeks later had also higher count of leukocytes, neutrophils, segmented neutrophils and ESR level relative to comparison group. It should be noted that in the early convalescence period elderly patients with coronary heart disease and COVID-19 had significantly elevated ESR, which confirms ongoing sustained inflammatory process. After evaluating the information content according to the calculated Kullback informativeness assessment for analyzed general blood test parameters, it was found to peak for platelet and leukocyte counts as well as ESR level. Thus, among the analyzed indicators in the general blood test, it turned out that platelet and leukocyte count along with ESR level were most informative and of prognostic significance during early convalescent period of elderly patients with coronary heart disease comorbid with a new coronavirus infection, which are proposed to be used as biomarkers of early convalescent period.

Background.In the absence of a vaccine against SARS-CoV-2, seasonal influenza vaccination during the pandemic contributed to lowered COVID-19 susceptibility and severity. The study was aimed to assess the state of post-influenza vaccination immunity, pneumonia frequency and severity in medical workers after using various flu vaccination regimens, between the 1st and 2nd peaks of COVID-19 epidemic rise.Materials and methods.Comparatively analyzed data on the levels of antibodies against influenza virus strains and pneumonia incidence in 487 medical workers was carried out: 1st group — unvaccinated in 2020–2021 (n = 281), 2nd group — vaccinated against influenza (Sovigripp), (n = 98), 3rd group — received combined vaccination against influenza and pneumococcus (Prevenar 13), (n = 108).Results.6 months after vaccination, the highest rates of influenza virus were detected in the A(H3N2), the level of seroprotection (≥ 1:40) ranged from 49.0% in unvaccinated (1st group) to 53.4–53.2% in those who received combined vaccination (group III), as well as influenza alone (2nd group), p 0.05; for strain A(H1N1) the level of seroprotection in 1st group is 24.5%, lower (p 0.04) than in 2nd group — 32.7%, but does not differ from the levels of 40.4% in group III; for strain B the level of seroprotection is the lowest ranging from 19.4% in the group of unvaccinated subjects up to 22.4% in 2nd group and 23.4% in 3rd group. The pneumonia incidence in 1st group (3.9%), 2nd group (3.1%), 3rd group (4.6%) did not differ, however, among all vaccinated subjects severity of pneumonia clinical course was mild, whereas in unvaccinated employees, except for mild course (45.4%, 5 out of 11 people) pneumonia in 36.4% (4 out of 11 people) cases was assessed as moderate and in 18.2% (2 out of 11 people) cases — severe with fatal outcomes.Conclusion.The study showed that 6 months after seasonal influenza immunization between the 1st and 2nd peaks of COVID-19 epidemic rise, the immunogenicity of the vaccine meets the CPMP criterion for the A(H3N2) strain. In vaccinated patients, the proportion of pneumonia with COVID-19 clinical picture was mild in 100% of cases, and in unvaccinated patients in 36.4% of cases — of moderate severity and in 18.2% — severe with fatal outcome.

Мета - на підставі опису основних симптомів клінічного випадку навести особливості діагностування ускладненої форми позалікарняної пневмонії в дитини старшого віку після перенесеного захворювання на COVID-19. Клінічний випадок. Описано клінічний випадок ускладненої форми позалікарняної пневмонії в дитини після перенесеного захворювання на COVID-19. 10-річний хлопчик захворів гостро з появи болю в грудній клітці та животі. Госпіталізований у тяжкому стані. Больовий синдром у ділянці грудної клітки був дуже сильно виразний та мав нападоподібний характер, переважно локалізувався в ділянці 3, 4, 5-го ребер. При цьому хлопчик займав вимушене положення - на правому боці з підігнутими ніжками. Біль був настільки інтенсивним, що дитина була блідою та шкіра лоба вкривалася потом. Висновки. У пацієнтів із COVID-19 найчастіше уражуються органи дихальної системи, що характеризуються стійкими респіраторними симптомами після гострого захворювання на COVID-19. Перелік клінічних ознак і симптомів не є специфічним для встановлення діагнозу позалікарняної пневмонії, що утруднює первинне діагностування та потребує введення до переліку обстежень додаткових методів діагностики. Під час загальноприйнятого загального аналізу крові, особливо для пацієнтів, які підлягають госпіталізації, слід визначати білки гострої фази. Саме ці білки слугують корисним інструментом для диференційного діагностування захворювання, здійснюють моніторинг за його перебігом і проведенням терапії. Хоча рутинним методом для діагностування захворювань органів дихання і досі вважають рентгенографію органів грудної клітки, ультразвукове дослідження легень є більш чутливим методом візуалізації, а також безпечним, особливо в обстеженні педіатричних пацієнтів із парапневмонічним плевральним випотом для визначення рідини в плевральній порожнині, кількості та подальшого моніторингу стану дитини. Вірогідність COVID-19, згідно з класифікацією СО-RADS, оцінюють за результатами комп’ютерної томографії в разі наявності чітких показань для цього методу дослідження, однак його не проводять для первинного діагностування уражень дихальної системи. Дослідження виконано відповідно до принципів Гельсінської декларації. На проведення досліджень отримано інформовану згоду батьків дитини. Автори заявляють про відсутність конфлікту інтересів.

The features of the hybrid law enforcement regime in the field of employment, labor and social protection are considered. Russia and the whole world have entered an era of turbulence, when customary and even emergency legal regimes that have been developed over decades do not allow us to respond effectively to challenges, regulate public relations and protect the rights and freedoms of legal entities in response to changes in the current situation. The traditional systematic approach to legal regulation using blocks of legislation formed in advance as a reaction to the situation changing in one direction or another often does not justify itself and each time requires a creative and individual, rather than template, approach from the law enforcement officer to the selection of used tools and norms of different legal regimes , which requires active rule-making to fill emerging gaps. Avoiding complex legal regulation adds originality to rulemaking and law enforcement in the early 2020s, the general direction of which is to accelerate the creation of rules of conduct in the field of labor, employment and social protection by increasing the role of the Government, speeding up the lawmaking process, expanding regional rulemaking, and giving greater legitimacy to the instructions of officials in comparison with documented acts. The legislator has consistently optimized the legal technique of preparing and adopting laws that meet the needs of operational support of a special military operation with labor legal means. The growth of regional rule-making in the field of social protection requires the elimination of shortcomings and unification at the federal level. A noticeable phenomenon was in a number of cases the replacement of written administrative acts with instructions from a senior official. The legal regimes formed in this way - aimed at countering the spread of the coronavirus COVID-19, accompanying the conduct of a special military operation, etc., can be called hybrid or constructed – assembled from various legal elements and do not form systems sufficient to achieve an integration-entropy balance. Moreover, for this design, elements of normatively established special legal regimes are used, which, however, have undergone significant transformation - a self-isolation regime instead of mandatory quarantine measures, special measures in the economic sphere instead of special economic measures established by presidential decree; mobilization – but partial. All this points to the 2020s as a period of hybrid law enforcement, when elements of other emergency regimes are used to construct the current law enforcement regime, but not in combination, while avoiding measures that entail a radical and total violation of civil rights and freedoms. At the same time, accelerated law-making clearly indicates that the array of norms that have been created over decades is insufficient to regulate the current agenda.

This article considers further development of the mathematical model that allows predicting the socio-economic situation and choosing the optimal management strategy in conditions of a mass disease. The model is a dynamic optimal control problem with a delay in phase variables. It takes into account social, biological and economic factors. The proposed modification of the model consists in simultaneous use of several quality criteria for evaluating management strategies, for which two approaches are proposed. The first approach is based on the reduction of criteria to same unit of measurement, which is the value of a statistical life. The second one consists of normalization of the criteria. Computational experiments were carried out using both modifications of the model; in particular, for the second approach, a series of calculations with different combinations of criteria significance was performed. The experiments used the values of the model parameters estimated on the basis of statistical data on the COVID-19 pandemic in the Russian Federation and the Ulyanovsk region. A modification of the numerical parameterization method developed by the authors was used to find a solution. The optimal solutions obtained for the Russian Federation and the Ulyanovsk region do not coincide when using the same objective functional. Such a result may indicate that it is desirable to choose a specific management strategy for each region.

The presented research covers a significant part of the period of the COVID-19 pandemic and studies the role of environmental factors in formation of population mortality from main causes. The main causes of mortality among the population of Odesa Region during the studied period include diseases of circulatory system, COVID-19, neoplasms, external causes, diseases of digestive organs and diseases of respiratory organs. The aforesaid causes constitute 94-95% of all causes of mortality in Odesa Region. However, out of these six classes of diseases, only diseases of circulatory system, COVID-19 and diseases of respiratory organs and some of their nosological forms have simultaneous peaks in mortality, during which mortality of the Odesa Region population from all causes almost doubles. Over time, there is a certain redistribution of frequency of the causes of mortality among the six main causing diseases of the population`s mortality in the region. But this does not explain occurrence of simultaneous peaks in mortality from diseases of circulatory system, COVID-19, and diseases of respiratory organs. Formation of simultaneous peaks in mortality from non-infectious and infectious diseases cannot be explained by the influence of social or anthropogenic factors. This indicates the need to address a number of environmental factors of natural origin – meteorological, biometeorological and heliocosmic. The study shows the possibility of an existing linear statistical connection between these environmental factors and the mortality of the Odesa Region population from such classes of diseases as diseases of circulatory system, COVID-19 and diseases of respiratory organs, as well as the relevant nosological forms. The results of the correlation analysis between mortality rates from major diseases and the environmental factors studied showed weak correlations between them. It is fully consistent with the World Health Organization's view of the role of environmental conditions in shaping public health.

The article analyzes the socio-demographic characteristics and value-worldview self-positioning of the distributors of conspiracy narratives (“conspiracy theories”) about vaccination against COVID-19 on the Russian social network “VK”. The research material consists of 33,674 profiles of VK users who published at least two messages during the pandemic that explicate the stated narrative. The collection and analysis of the material was carried out using big data analysis technologies. The purpose of the study is to determine whether it is possible to identify typical socio-demographic and ideological traits of anti-vaccer conspiracy theorists, which to a certain extent explain their penchant for conspiracy thinking. The results obtained refute the marginal dominance of conspiracy theorists in a pandemic situation. Versions popular in the scientific literature about the predominance of insufficiently educated people among “conspiracy theorists”, or the elderly as more gullible, or women as more suggestible, or residents of villages and small provincial towns as more conservative, etc. are not confirmed by the large-scale empirical studies of large user data. The results of the study may be useful for developing countermeasures and strategies to address public mistrust of institutions and official trends in public health, in particular vaccination policies. The traditional focus on information and educational measures (explanations about the dangers of the disease and the benefits of the vaccine) seems to be ineffective in the context of the emergence of value systems, cognitive distortions, general socio-political tension and other reasons that are still awaiting serious study.

In the time of fast technology growth, digitalization is transforming the landscape of many businesses. However, the antecedents of digital adoption within small and medium-sized enterprises in crisis are yet not fully understood. This study’s objective is to pinpoint factors that influence entrepreneurs’ intentions to utilize digital technologies in times of COVID-19 crisis in the Russian Federation. The study is based on the theory of planned behaviour. The analytical procedures performed on the data involved logistic regression modelling. This research draws on the Russian part of the 2021 Global Entrepreneurship Monitor Database (GEM) Adult Population Survey which measures the level and nature of entrepreneurial activity in different countries. Perceived behavioural control was revealed to be a key determinant of the intention towards digital technologies’ adoption – entrepreneur’s perception of opportunities and self-efficacy positively affects their intention to adopt digital technologies during a crisis. Notably, previous experience with digital technologies had a negative impact during the crisis. Further, an individual’s age inversely affects their tendency to pursue digital entrepreneurial initiatives. The research extends the theory of planned behaviour to volatile contexts and signals how entrepreneurs can adapt to upheavals during crises through digitalization, thus advancing understanding of entrepreneurial behaviour under extremities.

It has been established that 7.2% of patients hospitalized with coronavirus disease (COVID-19) exhibit signs of heart disease, with 23% of these patients experiencing heart failure. Currently, there is a lack of data on chest computed tomography (CT) for diagnosing myocarditis associated with COVID-19. The aim. To justify the feasibility and develop classification models for diagnosing myocarditis in COVID-19 patients based on chest CT data processing. Materials and methods. A retrospective analysis of data from 140 COVID-19 patients was conducted. Chest CT scans were analyzed using DRAGONFLY software, with permission from Object Research Systems. The COVID-CT-MD database, which includes CT data from 169 confirmed cases of SARS-CoV-2 infection, was used to build classification models. The regions of interest were fragments of heart CT images. Texture analysis methods were employed to create diagnostic models. Results. It was shown that the average density of the myocardium of a patient with a confirmed diagnosis of SARS-CoV-2 infection according to the Hounsfield scale does not essentially differ from the densitometric indicators of a healthy person. Therefore, the research was focused on finding structural changes in CT images for their use in constructing diagnostic models. The use of different classification algorithms had little effect on classification accuracy, probably due to the informational content of the input data. However, the obtained accuracy of the diagnostic models is acceptable and allows them to be used to support medical decision-making regarding diagnosis and treatment. Conclusions. Using classic methods, myocarditis was diagnosed in 7.1% of patients with severe pneumonia caused by the coronavirus. The global data closely aligns with the results of our clinical studies. The obtained results allowed for assessing structural changes in the myocardium characteristic of the acute form of SARS-CoV-2 infection. The constructed classification models indicate that specific changes in the myocardium during the acute form of SARS-CoV-2 infection can be identified using CT. The highest diagnostic accuracy on test samples reached 74%. The implementation of the developed diagnostic programs based on texture analysis of CT data and artificial intelligence technologies enables the diagnosis of myocarditis and the assessment of long-term treatment efficiency. Creation of these diagnostic programs using artificial intelligence technologies significantly simplifies the work of radiologists and improves the efficiency of myocarditis diagnosis in patients with SARS-CoV-2 infection.