Diagnosis of specific T cell immunity to the antigenic determinants of SARS-CoV-2 in patients seems to be an increasingly important task due to accumulation of data about the role of T cell immune response in course of coronavirus infection and clearance of SARS-CoV-2 in case of secondary infection. Previously, we designed the recombinant CorD_PS antigen for evaluation of T cell antiviral immunity, containing conservative and immunogenic sequences of structural proteins of the SARS-CoV-2 coronavirus. E. coli CorD_PS producing strain with stable expression of the recombinant CorD_PS antigen was obtained. Aim of the present work is to design a laboratory technology for the production of recombinant antigen CorD_PS, to control the quality of the obtained chimeric protein and to study its immunological activity. Development of the cultivation conditions for E. coli CorD_PS cells was carried out in conical flasks in LB-M_Km medium at 37 °C, then scaled in a fermenter with a volume of 30 liters. Expression was induced by the addition of IPTG. Expression was controlled in culture lysates in 12% SDS-PAGE. The resulting biomass was lysed using an ultrasonic disintegrator with followed by centrifugation. The compositions of lysing and solubilizing buffers were selected, as well as conditions for refolding of the recombinant protein. Cation exchange (SP-sepharose), hydrophobic (Butylsepharose) and exclusive (Sephacryl S-200 HR) chromatography were used sequentially to purify the dissolved protein. Protein impurities in the preparation were determined by reverse-phase HPLC and electrophoresis in 12% SDS-PAGE, residual lipopolysaccharides were determined using a gel-thrombin variant of the LAL test, residual proteins of the producer strain were determined by enzyme immunoassay, residual DNA of the producer strain was determined by binding with PicoGreen dye. Specificity was controlled by indirect enzyme immunoassay. The evaluation of cytokine production by CD4+T lymphocytes in response to their stimulation by recombinant antigen ex vivo was performed on a flow cytofluorimeter. The biomass yield during cultivation of E. coli CorD_PS in a 30L fermenter was up to 20 g/L for 4 hours of 0.1 mM IPTG induction. Sequential washing of inclusion bodies from bacterial cellular components and their subsequent solubilization in a buffer containing 8 M urea allowed to obtain a solution of denatured antigen with a concentration of 10 mg/mL. The efficiency of refolding by dilution was 75%. After three stages of chromatographic purification, protein samples with a concentration of 1.2-1.4 mg/mL, HPLC purity of 98.43%, corresponding to key quality parameters according to the OFS.1.7.1.0007.15, were obtained. The recombinant antigen showed specific binding to a sample of the First WHO International Standard and sample Company Reference Standard No. 3 of anti- SARS-CoV-2 human immunoglobulins in a specified concentration range. CD4+T lymphocytes effectively responded to recombinant antigen treatment by increasing IFNγ production. The optimal concentration of recombinant coronavirus antigen was 5 μg/mL. The developed technological process makes it possible to obtain 5-7 grams of coronavirus recombinant CorD_PS antigen in one cultivation cycle in 30 liters of fermentation medium with key quality parameters according to the OFS.1.7.1.0007.15. As a result of specific immunological activity studies of the recombinant coronavirus antigen CorD_PS, the concept of its possible use as a diagnostic tool for determining the formation of a T cell immune response was confirmed.

Purpose of the study: to study the dynamics of developing herd immunity against SARS-CoV-2 in the population of the Republic of Kyrgyzstan during COVID-19. Materials and methods. The work was carried out using the methodology for assessing population immunity developed by Rospotrebnadzor (Russia) as well as the Ministry of Health (Kypgyzstan) and the St. Petersburg Pasteur Institute. The selection of participants was carried out by questionnaire using a cloud (Internet server) service. To monitor population immunity, a cohort of 2421 subjects was formed, who participated in all stages of seromonitoring. Volunteers were randomized according to age groups (1–17, 18–29, 30–39, 40–49, 50–59, 60–69, 70+ years), regional and professional factors. Antibodies (Abs) against SARS-CoV-2 nucleocapsid (Nc) and the receptor binding domain (RBD) of S-glycoprotein were determined by qualitative and quantitative methods. The study was carried out in 3 stages according to a single scheme: 1st stage — 06/28–07/03/2021, 2nd — 21–25/02/2022 and 3rd — 31/10–04/11/2022. Since 2021, Kyrgyzstan has been vaccinating the population against SARS-CoV-2 mainly using inactivated whole-virion vaccines. Results. Population immunity against SARS-CoV-2 was predominantly accounted for by both Ab types (Nc+RBD+). By the 3rd stage, the percentage of such persons reached 99.2%, Nc–RBD– volunteers — up to 0.8%. At the 1st stage, middle-aged people dominated, but age differences were leveled out by the 2nd stage. The greatest impact on seroprevalence was found among medical workers, the smallest — among businessmen and industrial workers. Populational vaccination significantly impacted on the state of herd immunity that reached 25% by the 3rd stage. The refusals of the population in Kyrgyz Republic from vaccination noted at the 2nd and especially 3rd stages did not significantly affect level of herd immunity, which could probably be associated with asymptomatic cases of COVID-19, against which primary vaccination had a booster effect. Conclusion. The dynamics of population humoral immunity against SARS-CoV-2 included a number of changes in the level of circulating antibodies (Nc, RBD), caused by both primary infection and vaccination. The herd immunity formed in population of Kyrgyzstan allowed to reduce the incidence of COVID-19 to almost sporadic level.

Background. The course of the COVID-19 epidemic process depends on population immunity which prevents pathogen spread. Aim: to study an evolution of SARS-CoV-2 humoral immunity in the Belarusian population rela- tive to COVID-19 pandemic dynamics. Materials and methods. The work was carried out according to a methodology for assessing herd immunity developed by Rospotrebnadzor (Russia) and the Belarusian Ministry of Health involving the St. Petersburg Pasteur Institute (SPPI) by taking into account the WHO recommendations. The study was approved by the Bioethics Committee of Belarus and the SPPI Bioethics Committee. Participant selection was carried out by ques- tionnaire using a cloud (internet server) service. To monitor herd immunity, a cohort of 4661 subjects (involved at all stages of seromonitoring) was formed from the total volunteer group. Study subjects were randomized into groups based on age (117, 1829, 3039, 4049, 5059, 6069, 70+ years), geographic region, and occupation. For the detection of antibodies (Abs) against SARS-CoV-2 nucleocapsid (Nc) and S glycoprotein receptor-binding domain (RBD), rel- evant assay systems were used according to the manufacturers instructions. A four-stage study was conducted according to a unified scheme. Results. At stage 1 (pandemic month 15), herd immunity was mainly accounted for by Nc+RBD+ Ab status alone. By stage 2 (4 months later), its specific proportion decreased by 1.2-fold, whereas percentage of subjects solely bearing RBD-specific Abs increased by 1.7-fold. At stages 3 and 4 (9 and 19 months after the onset) vs. stage 2, percent- age of subjects with RBD+Nc decreased by 3.5%; the proportion of persons with Nc+RBD Abs increased by 1.5-fold. The most important contributor in herd immunity turned out to be due to population vaccination, with coverage reaching 70% by stage 4. Among vaccines, compared with whole-virion, inactivated BIBP-CorV vaccine the Sputnik V and Sputnik Light vector were used most often. Conclusion. The evolution of herd SARS-CoV-2 humoral immunity included a series of changes in circulating Ab levels (Nc, RBD). The hybrid immunity formed helped to reduce the incidence of COVID-19 to sporadic level.

Myocardial remodeling is well-known to be both an adaptive option under certain conditions of life (sports, pregnancy, etc.), and the result of cardiovascular pathology. The study of the features of cardiac remodeling includes the involvement of cardiomyocytes in the process by the level of troponins, creatine phosphokinase, and its cardiac isoform as markers of ischemia and necrosis. Also, neurohormonal rearrangement is evaluated using a natriuretic peptide, and endothelial dysfunction is determined using a C–reactive protein. The level of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) reflects the degree of the proteolytic activity and collagen fibers’ degradation. However, there are no clear biochemical markers of “adaptive heart” and pathological changes in different age periods, in the climatic environment, various types and severity of sports loads, especially when evaluating matrix metalloproteinases and their tissue inhibitors. The primary task in determining the criteria for pathological remodeling of the myocardium becomes the definition of normative indicators.The aim of the study was to determine the reference values of the main biochemical markers of cardiac remodeling in healthy adolescents living in the Far North. The levels of troponin I, creatine phosphokinase-MV, aspartate aminotransferase did not exceed the generally accepted standard values. There were correlations between lactate dehydrogenase, aspartate aminotransferase, and mass-growth indicators of adolescents. Markers of extracellular matrix degradation (MMP-9, TIMP-1 and TIMP-4, MMP-9/ TIMP-1) differed from the data available in the published studies, which is probably due to the influence of tissue hypoxia associated with the climatic living conditions and the age in children of the study group.

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

The study of the features and dynamics of the erythrocyte parameters of general blood analysis in patients with cardiovascular diseases who underwent SARS-CoV-2 associated pneumonia is of great practical importance. That was a prospective study. The study included 106 patients with SARS-CoV-2-associated pneumonia. All patients were divided into 2 groups. The first group included 51 patients without CVD, the second group included 55 patients with CVD .Patients in both groups underwent laboratory examination of blood samples at the time of hospitalization and 3 months after discharge from the hospital. Parameters of the erythroid series of the general blood test were assessed. Among inflammatory biomarkers, we examined the concentration of C-reactive protein (CRP), high-sensitivity CRP (hs-CRP) and homocysteine. Initially all patients underwent computed tomography of the chest organs. Revealed what indicators of the erythroid series in the groups of patients with and without CVD had significant differences in a number of parameters: ESR; RDW-SD and RDW-CV with significant excess of parameters in group 2. Three months after discharge from the hospital, patients in both groups had a significant increase in HCT, MCV, MCH. There was detected decrease in both groups in MCHC, RDW-CV (p<0.001 for all parameters), ESR level in group 2.At baseline, CRP exceeded reference values in both groups of patients, reaching maximum values in group 2. After 3 months CRP decreased significantly only in group 1. Increased CRP was associated with elevated hs-CRP in 3 months after discharge and elevated homocysteine levels in both groups, indicating the persistence of prolonged inflammatory vascular reaction in patients after SARS-CoV-2 associated pneumonia, more pronounced in group 2 patients. RDW-CV over 13.6 and lymphocytes / CRP less than 0.6 increase the likelihood of having lung tissue damage over 50% by 9.3 and 5.9 times, respectively. Thus, the data obtained confirm that RDW-CV, the coefficient of variation of erythrocyte distribution width, associated with the parameters of inflammatory response and the lymphocytes / CRP is lung volume marker and of COVID-19 severity. Careful consideration of already known laboratory parameters allows us to expand the number of indicators influencing the risk of COVID-19 complications and enable an earlier response to a difficult situation.

Objective: to study the seroprevalence of SARS-CoV-2 antibodies (AB) in children in the 2nd year of the COVID-19 pandemic in Russia. Materials and methods: prospective cohort study. The seroprevalence research was conducted among 3670 children aged 1 to 17 y/o from 26 modelling regions of Russia (that have been participating earlier in the five stages of seromonitoring during 2020-2021). The serological testing was carried out in December, 2021. The work was carried out according to a unified methodology set by the Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being with the Pasteur Institute of Epidemiology and Microbiology (Saint Petersburg, Russia). The plasma was obtained from 3 ml of venous blood, in which the level of AB to nucleocapsid (NC), and the SARS-CoV-2 receptor-binding domain (RBD) was determined by immunoferment method using reagents for qualitative and quantitative analysis. Results: the analysis of AB seroprevalence to NC and RBD showed the statistically significant increase in the share of seropositivity to RBD in children of all modelling regions (p<0.05). The most seropositive volunteers contained low levels of AB: 31.3-125.6 BAU/ml NC and 22.6-220 BAU/ml RBD. An increase in the level of AB to NC and RBD was accompanied by a decrease in the percentage of seropositive patients. Evaluating the contribution of children to the level of humoral immunity, convalescents (had been ill shortly before the examination), the “anamnesis” (had been ill at previous stages of seromonitoring) and asymptomatic (had been asymptomatically ill) groups were distinguished. The maximum contribution was made by children with asymptomatic cases of COVID-19 in anamnesis: in 82.3% (95% CI 81.1-83.6), of which 76.9% (95% CI 75.5-78.3) AB detected to RBD. The contribution of children of two other groups to the overall level of humoral immunity was 33 times less. Conclusion: statistically significant predominance of AB to RBD above AB to NC and their main contribution to the level of humoral immunity to SARS-CоV-2 (p<0.001).

The aim of this study was to characterize the genetic variants of HBV currently circulating in the Republic of Guinea, based on the nucleotide sequences of the complete virus genome, and to analyze clinically significant mutations in the Core and HBsAg regions during HBV monoinfection and HBV/HIV coinfection.Materials and methods. The study material was represented by 2616 blood serum samples collected from residents of the Republic of Guinea. The subjects were examined for the presence of HBV markers with a qualitative detection of HBsAg, HBs IgG, and HBCore IgG. HBV complete genome nucleotide sequences were obtained for 298 samples including HIV/HBV coinfected patients. Amplification and subsequent sequencing of HBV were performed using nested PCR with pair’s overlapping primers jointly flanking the complete HBV genome (S, P, C, X genes).Results. HBV serological markers were detected in 80.77% samples, while HBsAg was detected in 16.01% of the examined group. HBV DNA we detected in 22.36%. The prevalence of HBsAg-negative HBV in patients with HIV RNA is 45.16%, which is significantly higher than 6.07% found in the group without HIV infection. Phylogenetic analysis of HBV in the examined samples showed that HBV genotype E (75.5%) predominates in the group compared to HBV genotype D1 (9.39%), D2 (4.02%), D3 (6.37%), and A2 (4.7%). In the tested group, the variability of amino acids among the HBV samples was higher in the PreCore/Core region than in the PreS1/PreS2/S region. SHB mutations were detected in 83,89%, Core mutations in 94.29%, PreCore amino acid substitutions in 16.77% of the patients, respectively.The results obtained in this work demonstrate a high prevalence of HBV in the region and indicate the need for further largescale studies of HBV mutations in order to improve strategies for disease control and prevention in the Republic of Guinea.

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia Objective To study the role of therapeutic exercises (TE) in the correction of blood pressure, stiffness of the vascular wall, metabolic indices of body structure (volume, mass, area of visceral fat) and bone mineral metabolism in postmenopausal hypertensive patients. Methods. The study included 138 patients (mean age was 58.32 ± 7.61 years). All patients are divided into 3 groups. The first control group is 20 women without arterial hypertension and menopausе. The second group consisted of 58 patients with arterial hypertension (AH) and postmenopause who was not undergone complex of TE and the 3rd group - 60 women with AH and postmenopause who was undergone TE complex. Patients of all groups were examined in dynamics: at the starting point of the study and in 12 months after, ambulatory monitoring of blood pressure; sphygmography; densitometry and test for serum biochemistry parameters of blood samples, including sex hormones, vitamin D. Results. In the course of the study, blood pressure, vascular wall stiffness parameters, metabolic indices of body structure and disorder parameters of bone mineral metabolism were comparable in group 2 and 3 against the background of significantly reduced levels of sex hormones. Multidirectional correlation relationships between the studied parameters are revealed. The basic therapy in combination with therapeutic exercises led to a significant decrease in blood pressure and metabolic indices of body structure (p<.001) and to a persistent tendency of decrease the pulse wave velocity and increase of bone mineral metabolism in gr.3. Conclusion. The result of the study indicates that the exercise therapy complex used in the form of regular classes can be recommended for implementation in clinical practice with the aim of comprehensively affecting the patient’s body and developing personalized treatment tactics for postmenopausal women with hypertension.

OBJECTIVE:To study the role of therapeutic exercises (TE) in the correction of blood pressure, stiffness of the vascular wall and disorders of bone mineral metabolism in postmenopausal hypertensive patients.MATERIAL AND METHODS:The study included 78 patients (mean age was 53.32±7.61 years). All patients are divided into 3 groups. The first control group is 20 women without arterial hypertension and menopause. The second group consisted of 27 patients with arterial hypertension (AH) and post-menopause who were not undergone the TE complex and the 3rd group - 31 women with AH and post-menopause who were undergone TE complex. Patients of all groups were examined in dynamics: at the starting point of the study and 12 months later, out-patient monitoring of blood pressure; sphygmography; densitometry and test for blood serum biochemistry parameters, including sex hormones, vitamin D.RESULTS:In the course of the study, blood pressure, vascular wall stiffness and disorder of bone mineral density were revealed significantly higher in the group 3 with significantly reduced levels of sex hormones. Multidirectional correlation relationships between the studied parameters are revealed. Treatment combined with therapeutic exercises led to permanent improvement tendency in studied parameters like blood pressure, pulse wave velocity, metabolic disorders and T-criterion.CONCLUSION:The result of the study indicates that the exercise therapy complex used in the form of regular classes, according to the scheme proposed by the exercise therapy doctor, can be recommended for implementation in clinical practice with the aim of comprehensively affecting the patient's body and developing personalized treatment tactics for postmenopausal women with hypertension.

The study of the parameters of the lipid profile and markers of the inflammatory reaction of the vascular wall in patients with stable angina pectoris in the presence or absence of type 2 diabetes mellitus (T2DM) is of great importance for revealing the gender characteristics of the pathophysiological mechanisms of the development and course of diseases, developing secondary prevention of complications and determining the prognosis. 194 patients with stable angina pectoris (SA), single-vessel coronary artery disease, mean age 60.3 ± 7.8 years were examined. Patients were divided into two groups: group 1 - patients with SA without diabetes 2 (n = 152), group 2 - with SA and diabetes 2 (n = 42). In each group, subgroups of men and women are distinguished. The study of biomarkers was carried out upon admission to the hospital on the background of therapy, taken on an outpatient basis. The study included a complex of parameters of the lipid spectrum, markers of the inflammatory response, endothelial dysfunction, and carbohydrate metabolism parameters. A comparative analysis of biomarkers revealed an excess of reference values of atherogenic lipid fractions in both groups of patients, regardless of patient gender. Moreover, in the first group of patients, in the subgroup of women, a significant excess of the level of TC, PL (a), and ApoA-1 was registered compared with the subgroup of men. In the second group, there were no significant differences in parameters between the male and female subgroups. Evaluation of the parameters of the inflammatory reaction revealed in the subgroup of women with T2DM a steady tendency to exceed the level of hs-CRP, TNF-α, homocysteine compared with both men and women in the SA group without T2DM. The logistic regression revealed the main biochemical markers that affect the aggravation of the course of IHD in women with T2DM: this is a uric acid level of more than 380 mmol / l - OS 11.5 (95% CI 1.71-77.69), TNF-α more 8 pg / ml - OR 7.5 (95% CI 1.07-52.46) and an increase in TG - OR 3.33 (95% CI 1.073-10.335). Thus, women of the 2nd group with the presence of T2DM are characterized by the highest level of atherogenic fractions of lipids, markers of vascular inflammation, glucose and HbA1c, which may indicate the greatest potential for the development of atherothrombotic complications in this subgroup of patients.

The first case of COVID-19 was diagnosed in St. Petersburg on March 2, 2020; the period of increase in the incidence lasted for 10 weeks, the maximum rates were recorded in mid-May, and subsequently there was a statistically significant decrease in the incidence.Objective: to determine the level and structure of community immunity to SARS-CoV-2 among the population of St. Petersburg during the period of intensive spread of COVID-19.Materials and methods. Selection of volunteers for the study was carried out through interviewing and randomization. The exclusion criterion was active COVID-19 infection at the time of the survey. 2713 people aged 1 to 70 years and above were examined for the presence of specific antibodies to SARS-CoV-2. Antibodies were detected by enzyme immunoassay.Results and discussion. Studies have shown that in St. Petersburg, in the active phase of COVID-19 epidemic, there was a moderate seroprevalence to SARS-CoV-2, which amounted to 26 %, against the background of a high frequency (84.5 %) of asymptomatic infection in seropositive individuals who did not have a history of COVID-19 disease, positive PCR result and ARI symptoms on the day of examination. The maximum indicators of herd immunity were established in children 1–6 years old (31.1 %), 7–13 years old (37.7 %) and people over 70 years old (30.4 %). Differences in the level of seroprevalence in the age groups of 18–49 years are statistically significant. The highest level of seroprevalence was found among the unemployed (29.7 %), healthcare workers (27.1 %), education sector (26.4 %) and business sector personnel (25 %). In convalescents, COVID-19 antibodies are produced in 75 % of cases. In individuals with positive result of PCR analysis carried out earlier, antibodies are detected in 70 % of the cases. The results of the study of herd immunity to SARS-CoV-2 are essential to forecast the development of the epidemiological situation, as well as to plan measures for specific and non-specific prevention of COVID-19.

Objective. To assess efficiency of the “MIC-MICRO” kit developed in the Department of New Technologies of the Saint-Petersburg Pasteur Institute, on reference strains and clinical bacterial isolates. Materials and Methods. In order to assess the “MIC-MICRO” kit, several options of its execution were used, including different groups of antibiotics: aztreonam, amikacin, gentamicin, colistin, meropenem, nitrofurantoin, chloramphenicol, cefotaxime, ceftriaxone, ciprofloxacin, erythromycin. In order to determine the range of antibiotic values, the EUCAST-2020 database was used. The quality control of adsorbed antibiotics was carried out using reference strains: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213 and Escherichia coli NCTC 13846 (colistin-resistant). Acceptable and target ranges of MIC values for control strains are evaluated according to “Regular and extended internal quality control for determining MIC and disk diffusion according to EUCAST recommendations” (v10.0). A total of 28 clinical isolates of K. pneumoniae obtained from patients with nosocomial infections in St. Petersburg hospitals in 2018–2019 was used in the study. The coordination of test results was obtained in accordance with GOST R ISO 20776-1-2010. Susceptibility testing results were interpreted in accordance with EUCAST recommendations (v10.0). Results. The MIC values in relation to the reference strains obtained using the “MIC-MICRO” kit were determined in the range of recommended values of the EUCAST-2020 standard. The results obtained in relation to clinical isolates of K. pneumoniae showed that the sensitivity categories determined using the developed kit and the serial microdilution method were the same for all the studied strains. The percentage of colistin-resistant isolates (MIC > 2 mg/ml) in the serial microdilution method and determined using the “MIC-MICRO” kit was 35.7%. The percentage of susceptible strains was also similar for two types of methods (64.3%). Conclusions. Colistin susceptibility testing of K. pneumoniae strains using the “MIC-MICRO” diagnostic kit and the reference serial microdilution method in a tablet, showed comparable results. Diagnostic efficiency, ease to use and simple interpretation of results make it possible to use the developed “MIC-MICRO” kit in clinical laboratory practice.

Introduction. Growth Differentiation Factor 15 (GDF-15) is known to be an independent predictor of cardiovascular and all-cause mortality, as well as major bleeding in patients (pts) with non-valvular atrial fibrillation (AF). Since GDF-15 is expressed by a wide array of cells in response to inflammation and myocardial stress, it is interesting to study which clinical and functional parameters are most associated with the level of GDF-15 in pts with non-valvular AF and preserved left ventricular ejection fraction. Aim. To study the relationship of GDF-15 level in blood serum with parameters of clinical and functional status and to determine independent predictors of GDF-15 level in pts with non-valvular AF. Material and methods. 87 pts with non-valvular AF were studied, with an average age of 56.9±9.2 years. A general clinical examination, echocardiography and laboratory tests were performed, including fasting serum glucose (mmol/l),highly sensitive C-reactive protein (h/s CRP) (mg/l), creatinine level (mkmol/l) and subsequent calculation of glomerular filtration rate (ml/min/1.73m2), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (pg/ml). The level of GDF15 (pg/ml) in blood serum was determined using an enzyme immunoassay with the help of the human GDF-15/MIC-1 ELISA analytical kit (BioVender, Czech Republic). Results. The increase in the GDF-15 level was associated with ageing, ischemic heart disease, severity of arterial hypertension and heart failure, raising the risk of stroke, according to the scale CHA2DS2-VASc, disturbances of carbohydrate metabolism and obesity, increasing the levels h/s CRP and NT-proBNP, enlargement of the right and left atria, signs of diastolic left ventricular dysfunction and structural remodeling in the form of eccentric hypertrophy. Multiple linear regression analysis revealed 2 independent predictors of GDF-15 levels: age and fasting glucose. Conclusion. GDF-15 appears as an integral biomarker of age-related metabolic disorders and structural and functional changes in the heart, which opens up prospects for further study of its prognostic significance in pts with non-valvular AF.

Introduction. Growth Differentiation Factor 15 (GDF-15) is known to be an independent predictor of cardiovascular and all-cause mortality, as well as major bleeding in patients (pts) with non-valvular atrial fibrillation (AF). Since GDF-15 is expressed by a wide array of cells in response to inflammation and myocardial stress, it is interesting to study which clinical and functional parameters are most associated with the level of GDF-15 in pts with non-valvular AF and preserved left ventricular ejection fraction. Aim. To study the relationship of GDF-15 level in blood serum with parameters of clinical and functional status and to determine independent predictors of GDF-15 level in pts with non-valvular AF. Material and methods. 87 pts with non-valvular AF were studied, with an average age of 56.9±9.2 years. A general clinical examination, echocardiography and laboratory tests were performed, including fasting serum glucose (mmol/l),highly sensitive C-reactive protein (h/s CRP) (mg/l), creatinine level (mkmol/l) and subsequent calculation of glomerular filtration rate (ml/min/1.73m2), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (pg/ml). The level of GDF15 (pg/ml) in blood serum was determined using an enzyme immunoassay with the help of the human GDF-15/MIC-1 ELISA analytical kit (BioVender, Czech Republic). Results. The increase in the GDF-15 level was associated with ageing, ischemic heart disease, severity of arterial hypertension and heart failure, raising the risk of stroke, according to the scale CHA2DS2-VASc, disturbances of carbohydrate metabolism and obesity, increasing the levels h/s CRP and NT-proBNP, enlargement of the right and left atria, signs of diastolic left ventricular dysfunction and structural remodeling in the form of eccentric hypertrophy. Multiple linear regression analysis revealed 2 independent predictors of GDF-15 levels: age and fasting glucose. Conclusion. GDF-15 appears as an integral biomarker of age-related metabolic disorders and structural and functional changes in the heart, which opens up prospects for further study of its prognostic significance in pts with non-valvular AF.

The first case of COVID-19 was registered in the Leningrad Region on March 13, 2020. The period of increasing intensity of the epidemic process lasted 8 weeks. One month after reaching the maximum incidence rate, a study was organized to determine seroprevalence to COVID-19 among the population of the Region.Objective of the study was to determine the level and structure of community immunity to SARS-CoV-2 virus in the population of the Leningrad Region in the period of intensive COVID-19 transmission.Materials and methods. The work was carried out within the framework of the Rospotrebnadzor project on assessment of community immunity to the SARS-CoV-2 virus in the population of the Russian Federation. The content of antibodies to SARS-CoV-2 was determined applying ELISA using a kit for the analysis of human serum or blood plasma for the presence of specific IgG to the nucleocapsid of the SARS-CoV-2 virus , manufactured by the State Scientific Center of Applied Microbiology and Biotechnology (Obolensk) in accordance with the instructions for use.Results and discussion. The study has showed that the herd immunity of the population of the Leningrad Region was 20.7 %. The maximum level has been established in children 1–6 years old (42.3 %) and people over 70 years old (29.0 %). The highest level of seropositivity, except for children and older people, was found among the unemployed (25.1 %). The lowest level of seroprevalence was detected in civil servants (12.8 %) and military personnel (16.7 %). It has been shown that the risk of infection increases by 1.5 times in case of contacts with COVID-19 patients. After exposure to COVID-19 virus, antibodies are produced in 82.1 % of the cases. In individuals with a positive PCR test result obtained earlier, antibodies are detected in 82.8 % of cases. The share of asymptomatic forms among seropositive residents of the Leningrad Region was 86.9 %. The results of assessing the herd immunity to SARS-CoV-2 in the population of the Leningrad Region indicate that during the period of intensive COVID-19 transmission, an average level of seroprevalence was formed. A significant proportion of asymptomatic forms of infection characterizes the high intensity of the latently developing epidemic process. The results obtained should be taken into account when organizing preventive measures, including vaccination, and predicting morbidity rates.

Actual microbiological diagnostics of infections caused by Klebsiella spp. should include isolation of the strain, its identification and fastest possible determination of the pathogen susceptibility to antimicrobial agents. We evaluated the prospects of using MALDI-TOF mass spectrometry to determine the susceptibility of Klebsiella spp. strains to antimicrobial agents. According to the results of mass spectrometry Klebsiella spp. strains analysis, we carried out cluster analysis by the UPGMA method based on mass spectra and data on the susceptibility of the studied strains to antimicrobial agents, and then studied the obtained dendrograms. We identified the areas with the highest probability of the location of antibiotic resistance markers by comparing the mass spectra of susceptible and resistant microorganisms at different concentrations of antimicrobial agents. Thus, using MALDI-TOF mass spectrometry, a new direction in assessing the susceptibility of Klebsiella spp. to antimicrobial agents can be formed. Key words: antibiotic resistance, Klebsiella spp., MALDI-TOF mass spectrometry

Introduction . The HIV epidemic remains the most devastating in the history of mankind, despite comprehensive preventive measures. The HIV pharmacological resistance to several groups drugs at once is particular importance since this significantly reduces the therapy possibilities. Due to the low adherence to the treatment of patients certain categories, as well as the HIV drug-resistant transmission under various conditions possibility, treatment may not give positive results in 16–27% of patients who did not receive ART and in 50–70% of previously treated patients. The aim of our work was to evaluate the molecular-epidemiological structure and pharmacoresistant HIV variants in patients with antiretroviral therapy virologic failure in Arkhangelsk. Materials and methods. To evaluate the molecular-epidemiological structure and pharmacoresistant HIV variants in 76 HIV-infected patients with virologic failure of antiretroviral therapy from the Arkhangelsk region, HIV polymerase gene ( pol ) nucleotide sequences were analyzed. Results. In the examined group, HIV subtype A6 (IDU-A) prevailed (89,5%) compared with subtype B (9,2%), in one case (1,3%) the variant CRF03_AB was detected. For 86,8% of patients, resistance to any drugs was determined. Including resistance to protease inhibitors mutations — 33,3%, to revertase inhibitors — 92,4%. Isolates with pharmacoresistance only to NRTIs amounted to 16,6%, to NNRTIs 1,5%, to PI 10,6%, simultaneously to PI and NRTIs 12,1%, to NRTIs and NNRTIs 46,96%, to all three groups of drugs at the same time — 12,1%. The most common mutations are drug resistance to lamivudine and emtricitabine (M184V), nevirapine and efavirenze (K103N, G190S), thymidine analogs (T215F/Y and/or K219Q/E and/or D67N), and non-thymidine L nucleoside analogues).

Allergen-specific diagnostics is carried out on the basis of the data collection from the patient’s family and personal history, skin test results, provocative tests and laboratory research methods. Methods for determining specific IgE antibodies (sIgE) play a key role in confirming the diagnosis and identifying the pathogenetic mechanism of an immediate-type hypersensitivity to an allergen. The purpose of the study was to evaluate the results of determining sIgE for allergens of cat epithelium, house dust mite D. farinae and birch pollen in the blood serum of patients suffering from respiratory allergy, by comparing two methods of ImmunoCAP Phadia and 3gAllergy Immulite, as well as determining whether the results of these test systems are in concordance with the results of skin tests in the patients. The serum samples were obtained from patients of St. Petersburg adult outpatient clinics, who suffered from respiratory allergies (n = 50). The samples were analyzed in parallel in two laboratories, with each of the laboratories using single test systems. The retrospective skin test results were obtained from twenty six of the fifty selected patients. The inter-method comparison was conducted by determining the concordance of positive and negative results, correlation and regression analysis of sIgE results for each allergen and ROC-analysis to compare the diagnostic specificity and sensitivity of test systems in relation to the results of skin tests. This study showed that, in terms of agreement and contingency of the results, the Immulite test system had a close relationship with the Phadia test system. Both analysis of classes and quantitative sIgE analysis showed a good positive correlation from 0.79 to 0.99 (p < 0.0001) between the two test systems for all three allergens. High accuracy of coincidence in terms of sensitivity, area under the ROC curves (AUC) and cut-off threshold in both test systems was obtained for the D. farinae allergen. For allergens of cat epithelium and birch pollen, some differences between test systems were observed, i.e., sensitivity and AUC values were significantly higher in Immulite than in Phadia assay for both allergens.Thus, the inter-method comparison gave almost equivalent binary and quantitative results of the determination of sIgE antibodies to cat, tick and birch allergens. Comparison of in vitro test results, and their correlation with skin tests showed that the cat and birch in vitro antibody testing with Immulite assay was more closely connected with skin test results, than Phadia assay system.

The gut microbiota of healthy people, living in different regions, may vary considerably. The article presents the results of comparative qualitative and quantitative study of the intestine aerobic and anaerobic microbiota of residents of the Republic of Guinea (46) and Russia (60). The content of microorganisms (Enterobacteriaceae, Enterococcus spp., Lactobacillus spp., Bifidobacterium spp., Staphylococcus spp., Candida spp., non-fermentative gram-negative bacteria and others) in 1.0 gram of faeces was determined by bacteriological methods. Generic and species identification was performed using Vitek 2 Compact (bioMerieux, France), tube biochemical tests and MALDI-TОF mass spectrometry (Bruker Daltonics, Germany). Pearson χ2 criterion, p < 0.05 and Fisher’s exact test (medstatistica.ru) were used to assess the differences in the compared groups. 95% confidence intervals were calculated by the method of Wilson. Microbiological disorders were characterized by a decrease in the number of obligate microorganisms, an increase in the number of facultative (opportunistic) microorganisms (above 106 CFU/g) and the emergence of their associations. Dysbiotic disorders were identified in both compared groups: in 100% patients from Republic of Guinea (95% CI:92.3–100) and in 86.7% patients from St. Petersburg (95% CI:75.8–93.1). Severe degree of microbiota disorders in the residents of the Republic of Guinea was revealed at 19.6% (95% CI:10.7–33.2), in group of residents of St. Petersburg in 9.6% (95% CI:4.2–20.6). In both groups the microbiota disorders of third degree were detected less frequently, compared with the microbiota disorders of second degree. The study has found no significant differences in the content of obligate bacteria (Bifidobacterium spp. and Lactobacillus spp.), however, significant differences in the species composition of the facultative part of the microbiota were revealed. The residents of the Republic of Guinea had “atypical” E. coli (lactosonegative and hemolytic) and non-fermenting gram-negative bacteria Comamonas kerstersii more frequently. Opportunistic microorganism associations have been found in 30.4% of the residents of the Republic of Guinea (95% CI:19.1–44.8) and 18.3% of residents of St. Petersburg (95% CI:10.6–29.9). Opportunistic microorganism associations from the residents of the Republic of Guinea always contained Staphylococcus aureus. It is necessary to conduct further research on a bigger population to access the differences in the compared groups in Staphylococcus aureus and Hafnia alvei.