Features of the Humoral Response to Infection, Vaccination, and Revaccination during COVID-19.

IgM and IgG antibodies to the SARS-CoV-2 virus are detected in subjects who have recovered from COVID-19; IgM antibodies persist in a 1/3 of infected subjects up to 12 months from the moment of the disease, while IgG antibodies are present in the vast majority of cases (97%; medium and high levels antibodies were registered in 85% of cases). By the 12th month, 40% of those who recovered still have a very high level of IgG antibodies to the S-protein (>500 BAU/ml). In the feces, urine, and blood serum of patients with long-term persistent IgM antibodies, no coronavirus antigens were detected. After vaccination with the Gam-COVID-Vac vaccine, IgG antibodies to the S-protein are detected in 100% of cases and remain at a high level for 4 months, by the 5-6th month, the level of antibodies decreases. During revaccination, the level of IgG antibodies to S-protein reaches high values earlier than during primary vaccination, and remains high for 4 months (observation period). The blood sera of recovered and vaccinated patients have a high virus-neutralizing activity (at least 1:80), while its level is somewhat higher in recovered patients.

[Discriminant analysis in establishing the relationship of pathogenetic mechanisms of gestational complications in urogenital infection in pregnant women.] / Дискриминантный анализ в установлении взаимозависимости Ð¿Ð°Ñ‚Ð¾Ð³ÐµÐ½ÐµÑ‚Ð¸Ñ‡ÐµÑÐºÐ¸Ñ Ð¼ÐµÑ Ð°Ð½Ð¸Ð·Ð¼Ð¾Ð² развития Ð³ÐµÑÑ‚Ð°Ñ†Ð¸Ð¾Ð½Ð½Ñ‹Ñ Ð¾ÑÐ»Ð¾Ð¶Ð½ÐµÐ½Ð¸Ð¹ при урогенитальной инфекции Ð±ÐµÑ€ÐµÐ¼ÐµÐ½Ð½Ñ‹Ñ .

The aim of the work - to establish the interconnection and interdependence of toll-like mediated pathogenetic mechanisms of urogenital infection in pregnant women from the position of epigenomics. Using discriminant analysis in 89 patients with urogenital infection in pregnant women for the first time was established a reliable evidence-based relationship and interdependence between mucosal immunity, the severity of the infectious process, clinical manifestations, symptoms of miscarriage in the background of simultaneous development of the infectious process and pregnancy. For urgent delivery (infection), urgent childbirth (infection and clinical manifestation) and premature birth, mucosal immunity determines the severity of anti-infective resistance (with increasing mucosal immunity oppression of infectious process and clinical manifestations is logged , and its decrease increases the severity of infection process and clinical manifestations); the inhibition of mucosal immunity prevails over its hyperreaction (inhibition of mucosal immunity is determined by the physiological immunodepression in response to the development of pregnancy, as well as in response to herpes virus infection when activated); the severity of the infectious process depends on the severity of clinical manifestations and symptoms of miscarriage. During miscarriage mucosal immunity provides the pathophysiological course of infectious process and the clinical manifestations and development of symptoms of misacrriage; increasing levels of mucosal immunity to hyperreaction contributes to the development of symptoms of abortion and miscarriage; not registered mutual influence of oppression, mucosal immunity and its hyperreaction; the severity of the infectious process does not depend on the severity of clinical signs and symptoms of miscarriage. In urgent childbirth (infection), the oppression of mucosal immunity does not affect the severity of clinical manifestations, symptoms of abortion and the infectious process. In urgent or premature birth, and termination of pregnancy, the oppression of mucosal immunity affects the severity of clinical manifestations, the severity of the infectious process and the symptoms of abortion; the severity of clinical manifestations and the severity of the symptoms of abortion are interrelated. In urgent birth (infection) mucosal immunity overreaction affects the severity of clinical manifestations, symptoms of miscarriage and infection; in case of term and preterm labour overreaction mucosal immunity on the severity of infection and symptoms of abortion and does not affect the severity of clinical manifestations and at the termination of a pregnancy mucosal immunity on the severity of the infectious process and does not affect the severity of clinical signs and symptoms of abortion. The levels of mucosal immunity inhibition, its hyperreaction, clinical manifestations, symptoms of pregnancy termination and the severity of the infectious process do not depend on the type of herpes simplex virus. In the absence of infection with herpes simplex virus in patients with urogenital infections of pregnant women, there is no mutual influence and the relationship between the oppression of mucosal immunity and hyperreaction of mucosal immunity, the oppression of mucosal immunity prevails over its hyperreaction. With increasing mucosal immunity oppression, increased anti-infectious resistance of the body (the decreased activity of the infectious process), and with its decrease decreased (increased activity of the infectious process). Hyperreaction of mucosal immunity influenced the severity of pregnancy termination symptoms, clinical manifestations and infectious process, and also determined the severity of pregnancy termination symptoms. The severity of the infectious process and clinical manifestations influenced the symptoms of abortion. The severity of the infectious process did not affect the clinical manifestations. During infection with herpes simplex virus type I or type I and II on the background prevalence of oppression mucosal immunity over hyperreaction mucosal immunity, the presence of relationships between them, and the impact of mucosal immunity on the severity of the infectious process and the clinical manifestations increase mucosal immunity has been shown to decrease the severity of infection and clinical manifestations (reduction of anti-infective resistance), while reducing mucosal immunity the severity of infection and clinical manifestations increased. Hyperreaction of mucosal immunity influenced the severity of pregnancy termination symptoms and determined the severity of pregnancy termination symptoms. The severity of the infectious process and clinical manifestations influenced the symptoms of abortion. The severity of clinical manifestations reflects the severity of the infectious process. In type I and type II of pregnancy, the level of mucosal immunity determines the anti-infectious resistance of the body in urogenital infection of pregnant women. Inhibition of mucosal immunity and its hyperreactions are interrelated, have an impact on each other, as a result of their integral interaction, increasing the levels of mucosal immunity leads to a decrease in the severity of clinical manifestations and the infectious process, reducing the levels of mucosal immunity contributes to the manifestation of clinical manifestations, as well as increasing the severity of the infectious process. Hyperreaction of mucosal immunity affects the severity of symptoms of abortion, infection and clinical manifestations. The infectious process and clinical manifestations determine the severity of the symptoms of abortion. In type III and type IV of pregnancy course, there is no mutual influence of mucosal immunity oppression and its hyperreaction. The levels of indicators of mucosal immunity oppression and its hyperreaction are interrelated; the increase in the severity of mucosal immunity oppression is accompanied by a decrease in clinical manifestations and severity of the infectious process and vice versa. Hyperreaction of mucosal immunity affects the severity of symptoms of abortion, infection and clinical manifestations. The infectious process determines the severity of the symptoms of abortion and clinical manifestations, acting as a leading component of gestational complications in urogenital infection of pregnant women. In the III type of pregnancy course oppression of mucosal immunity does not affect the severity of symptoms of miscarriage. In the IV type of pregnancy course, the levels of mucosal immunity oppression prevail over the indicators of mucosal immunity hyperreaction, which is due to the integral interaction of physiological inhibition of immunological reactivity of the organism in response to pregnancy and inhibition of immunological reactivity of the organism, accompanying the activation of infectious process of viral genesis. Hyperreaction of mucosal immunity determines the symptoms of abortion.

[Efficacy of laboratory methods of diagnostic of purulent bacterial meningitis.]

According to the World Health Organization, every year about 1 million cases of purulent bacterial meningitis (PBM) are registered in the world, of which 200 thousand cases end in death. Bacterial meningitis is polyethiologic, which makes the task of determining the pathogen the main in the organization of epidemiological surveillance, treatment regimens, planning of preventive and anti-epidemic measures. The quality of laboratory diagnostics has a key influence on this. The true incidence of meningitis of different etiology can be altered at low-efficiency laboratory diagnostics. This work was carried out to assess the effectiveness of existing laboratory methods for the detection of PBM pathogens: Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis; as a part of the programme on sentinel surveillance of invasive bacterial diseases (IBD) carried out by the WHO regional office for Europe in a number of countries in Europe (Ukraine, Belarus), Transcaucasia (Azerbaijan, Armenia, Georgia), Asia (Uzbekistan, Kyrgyzstan, Kazakhstan) in the period 2010-2017. 2893 samples of clinical material (CSF and blood) obtained from patients with the meningeal syndrome were studied by four diagnostic methods: cultural method, latex-agglutination test, immunochromatographic test (BinaxNOW), PCR (conventional and real-time), used to identify the following pathogens: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae. When identifying the causative agents of BM, PCR more effective than culture method is 5 times in detecting N. meningitidis; 3 times in the detection of S. pneumoniae; 4 times the detection of H. influenzae b. Latex-agglutination test and immunochromatographic test allow to increase the identification of pathogens of BM for N. meningitidis - by 35.6%; S. pneumoniae - by 67%; H. influenzae b - by 19.2%, it is possible to set them in the field and at the epidpoint if necessary. When working with clinical material from patients diagnosed with GBM, it is advisable for bacteriological laboratories to complement the culture method of microbiological diagnosis of latex-agglutination test, immunochromatographic test or PCR.

[Quantitative and qualitative composition of axilla microbiota in practically healthy individuals].

AIM: Characteristics of quantitative and qualitative composition of cultured microorganisms isolated from axilla skin of practically healthy individuals. MATERIALS AND METHODS: 77 practically healthy individuals aged 18 to 40 years were examined. Species identification of microorganisms was carried out byculture-morphologic, tinctorial and biochemical properties using time-of-flight mass spectrometer and rpoB gene amplification with subsequent direct sequencing. RESULTS: Quantitative evaluation of microbial composition of axilla skin microbiota in most of the practically healthy individuals varied in the 4-5 lg CFU/ml interval, whereas seeding of skin by this microbiota at the level of 8 lg CFU/ml was not detected. 158 strains of 24 microorganism species were identified in this biotope. Most of these strains (68.9%) belonged to Corynebacterium genus, 21.6% of strains--to Staphylococcus genus, 7.6% of strains--to Micrococcus genus and 1.9% of strains--Candida albicans. 16 species of corynebacteria were isolated with predomination of C. tuberculostearicum (40.3%), C. amycolatum (18.4%) and C. ureicelerivorans (14.8%) strains. The microbial landscape in most of the examined individuals (77.9%) was presented by microorganism association. CONCLUSION: Quantitative and qualitative species composition of cultured microorganisms isolated from axilla skin biotope of practically healthy individuals was characterized for the first time.

[Comparative analysis of informative-diagnostic properties of mucosa immune-reactivity parameters].

AIM: Study the features of immune-reactivity expression in mucosa depending on their topicity and etiopathogenesis of the pathological process. MATERIALS AND METHODS: Data from 30 clinically healthy children and 77 children with acute and recurrent diseases of respiratory tract: 51--with acute and 15--with chronic bronchitis; as well as 132 women: 41--with active stage of acute urogenital chlamydia infection, 29--with recurrent chronic process, 30--with non-recurrent form and 32 clinically healthy women were analyzed. Saline and urogenital tract mucosa discharge was analyzed for IgG, sIgA and secretory component, IL-1beta, 4, 6, 8, 9, 10, 12, IFNgamma, TNFalpha and GM-CSF, TLR-2, TLR-3, TLR-4, TLR-8 gene expression levels as well as content of lysozyme, total protein and leucocytes. RESULTS: Solidity, universality and practically single-stage triggering of mucosa immune reaction mechanisms to intervention by foreign agents regardless of their localization was confirmed. A dependence of immune-reactivity expression on the form of pathologic process, its localization and qualitative and quantitative characteristics of the infectious agents was clearly seen. The highest level of clinical-laboratory and immunological parameters is inherent for patients with acute processes in urogenital tract (cervical canal and urethra), especially cause by mixed infections. CONCLUSION: Immune diagnostic parameters of mucosa among which TLR system is especially notable have high information properties allowing not only diagnostics of inflammatory process but also differentiating its form and character our course.

[Molecular-genetic and phylogenetic characteristic of Streptococcus pneumoniae strains isolated from patients with meningitis and carriers].

AIM: Analyze genetic and phylogenetic interrelations between S. pneumoniae strains isolated from meningitis patients and carriers. MATERIALS AND METHODS: 23 S. pneumoniae isolates (9 from bacterial meningitis patients, 9 from nasopharynx of bacterial carriers, 5 strains from museum collection of Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology) were studied. S. pneumoniae ATCC 49619, S. mitis ATCC 49456 served as control strains. S. pneumoniae serotype determination was carried out in latex-agglutination reaction and quelling reaction. Multiplex PCR according to WHO protocols was used for molecular-genetic study and pneumolysin (ply), autolysin (lytA), surface cellular adhesin A (psaA) and capsule polysaccharide (cpsA) gene determination. Multilocus sequence-typing was carried out according to WHO scheme for 7 "housekeeping" segments--aroE, gdh, gki, recP, spi, xpt and ddl. Computer programs from available internet resources were used for data processing and dendrogram building. RESULTS; The S. pneumoniae isolates analyzed were established to belong to 19 sequence types that may be combined into 4 subclusters. Results of molecular-genetic and serologic typing were completely comparable. CONCLUSION: Attribution of isolates from the same serotype and serogroup to different sequence-types gives evidence on the ongoing changes within serotype and as a result changes in allele profile of circulating S. pneumoniae isolates. Membership of isolates in separate subclusters gives evidence on close evolution relationship between isolates obtained from patients with bacterial meningitis and carriers. Certain isolates had not previously been registered in Russia and were probably imported from the territories of other countries.

[The phylogenetic position of Chlamydia strains isolated from monkeys and humans with Chlamydial pathology in the family Chiamydiaceae. Genotypic and phenotypic properties of this pathogen].

Based on the results of the comparative analysis concerning relatedness and evolutional difference of the 16S - 23S nucleotide sequences of the middle ribosomal cluster and 23S rRNA I domain, and based on identification of phylogenetic position for Chlamydophila pneumoniae and Chlamydia trichomatis strains released from monkeys, relatedness of the above stated isolates with similar strains released from humans and with strains having nucleotide sequences presented in the GenBank electronic database has been detected for the first time ever. Position of these isolates in the Chlamydiaceae family phylogenetic tree has been identified. The evolutional position of the investigated original Chlamydia and Chlamydophila strains close to analogous strains from the GenBank electronic database has been demonstrated. Differences in the 16S - 23S nucleotide sequence of the middle ribosomal cluster and 23S rRNA I domain of plasmid and non-plasmid Chlamydia trachomatis strains released from humans and monkeys relative to different genotype groups (group B- B, Ba, D, Da, E, L1, L2, L2a; intermediate group - F, G, Ga) have been revealed for the first time ever. Abnormality in incA chromosomal gene expression resulting in Chlamydia life and development cycle disorder and decrease of Chlamydia virulence can be related to probable changes in the nucleotide sequence of the gene under consideration.

[A novel view of prophylaxis and treatment of chronic adenoiditis in children].

The present clinical study had the objective to evaluate the role of a hypertonic solution of sterile water from the Adriatic Sea in the prevention and treatment of chronic adenoiditis in children. It included 30 children aged from 2.5 to 15 years. The control group was comprised of 30 children treated by intransal drop infusion of physiological saline followed by irrigation of the nasal cavity with framicetin as recommended by the manufacturer. The study failed to reveal a significant difference (P > 0.05) between dynamics of the symptoms of chronic adenoiditis in the patients of either group assessed based on the 10-point analog visual scale. However, the frequency of relapses of adenoiditis during the observation period (3 months) was significantly lower in the patients treated with the hypertonic solution of sterile seawater. Microbiological investigations of the material from the pharyngonasal cavity showed no difference between the occurrence of tansient bacterial microflora in the patients of the study and control groups.

[Colonization resistance and immunological reactivity of children's oropharyngeal mucosa in health and bronchopulmonary pathology].

The study group was comprised of 27 practically healthy children, 51 patients with acute bronchitis, 15 with chronic bronchitis and 11 with pneumonia. It was shown that changes of microbiocoenosis in back of the throat (BOT) were related to increased mucosal contamination with normal microflora and opportunistic microorganisms. The highest degree of contamination was observed in children with acute bronchitis. Normocoenosis was detected only in 13 practically healthy children. The disorders of microbiocoenosis took the form of disbiosis and acute inflammatory processes in patients with acute and chronic bronchitis and pneumonia. However, the large amount of normal flora together with the high Ig level ensured marked colonization resistance as evidenced by the values of natural colonization coefficient of nasopharyngeal epithelium (NCCNE) and balance coefficient (BC). These data suggested development of compensated secondary immunodeficiencies. In patients with acute bronchitis and pneumonia, local synthesis of Ig prevailed. It is shown that BC can be used to screen children for disorders of mucosal immunity. The presence of increased saliva IgE levels in patients with acute and chronic bronchitis supports the generally accepted concept of bronchi as a "shock organ" in allergic condition. It was demonstrated that IgE levels in saliva increase earlier than in serum and may be used as a prognostic criterion in patients with bronchopulmonary pathology.

[Molecular mechanisms of induction of innate immunity].

Cellular and molecular mechanisms of congenital immunity at different levels are discussed including single cell expression patterns and intracellular localization of individual TLR, the use of adapter molecules for generation of activation signals in response to microbial and non-microbial pathogens, soluble trap receptors, and intracellular negative regulators.

[Oral cavity microflora in patients with non-specific ulcerative colitis and Crohn's disease].

Results of study of microecological disorders in oral cavity of patients with non-specific ulcerative colitis (NSUC) and Crohn's disease (CD) and control subjects (patients with hypertension). Condition of mucosa was assessed on the basis of morphological data and electrophoretic mobility of cell nuclei, whereas structure of microbiocenosis and metabolic activity of microflora--on the basis of saliva bacterial culture and contents and profile of volatile fat acids in it. Detection rate of negative charge of the cell nuclei (decrease of functional activity of epithelium) was significantly higher in patients with NSUC and CD (66.6%) compared with controls (10%). This fact was directly related with hypercolonization of oral cavity by Gram-negative microflora. Lesions of mucosa which are characteristic of NSUC and CD and determined by pathologic immune mechanisms correlated with quantity of pathogenic microflora (Staphylococcus aureus and Candida). Marked differences of chromatograms' patterns were observed in patients with NSUC and CD indicating the suppression of anaerobic microflora in patients with CD and hypercolonization of oral cavity by anaerobic microflora in majority of patients with NSUC.

[Modern methods of laboratory diagnostics of Chlamydia infections].

Need for further improvement of methods for verification of etiological agent of urogenital and respiratory chlamydiosis on the basis of increased biotechnological requirements to antigens for serological reactions, primers for PCR assay (refinement of connection of primers with microorganism's zones of genome most significant for its life activity or formation of most diagnostically significant complexes of primers), and selection of cultivating conditions considering the predicted features of clinical strains of the agent was substantiated.

[The microflora of vaginal, gutter, and intestinal bioptats of women with a threat of early miscarriage].

A complex simultaneous assessment of the microbiota (the aerobic and anaerobic links as well as the parietal and lumen components) of the gutter, vagina, and intestines of women with a pathological pregnancy was performed. In 30% of women the study revealed system dysbiotic changes. Local immune reactivity was decreased, which may be considered a provoking factor. In conclusion, complex microbiological examination makes it possible to objectivize the picture of the pathological process and its outcome. A criterion for the administration of correcting measures is offered.

[Strategic aspects of constructing probiotics of the future].

The publication systematizes modern achievements in understanding the role of microbiocenoses in the existence of macroorganism, and possible ways of constructing of probiotics of the future.

[The role and biological significance of toll-like receptors in the anti-infectious resistance of the organism].

Modem conceptions of the role of toll-like receptors (TLR) in the innante immunity mechanisms realization and data on the interaction between TLR and pattern-associated molecular proteins of microbial or endogenic origin are presented in the review.

[Protease activity of microflora in the oral cavity of patients with periodontitis].

Microbial spectrum and non-specific as well as specific IgA1 protease activity of isolated microorganisms were investigated in gingival liquid of patients with periodontitis. Microorganisms from the gingival liqud of these patients belonged to conditional-pathogenic obligate and facultatively anaerobic bacteria. 24 strains of microorganisms have been identified. Nonspecific proteolytic activity was found in the following microorganisms: Actinomyces israelii, Actinomyces naeslundii, Aerococcus viridans, Bifidobacterium longum, Neisseria subflave, Streptococcus parvulus, Eubacterium alactolyticum, Lactobaccilus catenoforme, Bacillus spp. Specific IgA1-protease activity and lack of proteolytic activity towards IgG was found in Streptococcus acidominimus, Streptococcus hansenii, Streptococcus salivarius, Leptotrychia buccalis, Staphylococcus haemolyticus and Neisseria sicca. No proteolytic activity was found in cultivation medium of Eubacterium alactolyticum (1 strain), Prevotella buccalis, Aerococcus viridans and Streptococcus sanguis.

[Microbiologicaland immunological criteria for estimation of ureaplasmosis treatment efficacy in women].

The role of surface and parietal vaginal microbiocenosis and immunoglobulins in development of infectious process, in prediction of resistance of causative microorganism to antibiotics and treatment efficacy was demonstrated on group of women with ureaplasmosis. Evaluation of anaerobic part of vaginal microbiota contemporary with its aerobic part reliably increased informative value of microbiological test in women with urogenital diseases. There are reasons to include interferon preparations into the complex therapy of ureaplasmosis.

[Tertiary peritonitis: aspects of prophylaxis].

Thirteen patients with generalized purulent peritonitis were treated with multiple staging sanation of abdominal cavity and special bacteriophages with high activity to 4 nosocomial bacterium strains. The phages permitted to prevent infection with these nosocomial strains. Three new phages with high bacteriolytic activity were identified. Antibacterial activity "in vitro" of all phages was higher than antibiotic susceptibility. It is concluded that bacteriophages are promising method of treatment and prevention of complications associated with nosocomial infection at surgical patients with long-time purulent processes.

[The microbiological and immunological characteristics of disbiotic disturbances of the biotopes of the mucose membranes of the respiratory and urogenital tracts].

The study consisted in comparison of the microecology and the parameters of the humoral immunity of the biotopes of the respiratory and urogenital tracts under normal conditions and in inflammatory processes caused by bacterial agents. The study revealed significant changes in the microbiocenosis of the respiratory and urogenital tracts, caused by decline of indigenous microflora and increase of the content of conditionally pathogenic microorganisms. These changes depended on the degree of the infectious process severity. Measurement of the humoral immunity parameters revealed a significant correlation between the content of conditionally pathogenic microorganisms and the levels of M and A immunoglobulins, as well as secretory IgA and free secretory component (sc) in the vaginal secretions of patients with non-specific inflammatory diseases of the genital tract, as well as G and A immunoglobulins, secretory IgA, and sc in the saliva of patients with chronic inflammatory diseases of the respiratory tract.

[Microecology and humoral immunity characteristics of the vagina in women with nonspecific inflammatory diseases of the genitals].

The complex cytological, microbiological and immunological examination of 90 female patients with nonspecific inflammatory diseases of the genital tracts and 30 clinically healthy women (the control group) was carried out. The examination revealed significant microbiocenosis changes in the lumen and the parietal area of the vagina, depending on the severity of the infectious process: a decrease in the level of lactobacilli, an increase in the content of opportunistic facultative anaerobic microorganism in the lumen and obligate anaerobic bacteria in the parietal area. Pronounced correlation between the content of opportunistic microorganisms and the levels of IgM and IgA, as well as secretory IgA and free secretory component in vaginal secretions in patients in patients with non-specific inflammatory diseases of the genital tracts has been revealed.