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The impact of the new coronavirus COVID-19 infection on the course of pregnancy, maternal and child health is largely unclear and controversial. The presented literature review analyzes changes in the immune, cardiovascular, and endocrine systems in women in physiological pregnancy. The peculiarities of the course of infection caused by SARS-CoV-2 virus in pregnancy, depending on the virus variant, are presented, the issues of infection pathways into immune and non-immune cells, including placental cells, as well as the issues of transplacental transfer of the virus – the key moment of infection of the embryo or fetus, on which the outcome of pregnancy also largely depends, are considered. Promising approaches to COVID-19 therapy are presented: use of inhibitors of transmembrane serine protease 2 (TMPRSS2), furin, angiotensin-converting enzyme (ACE2) and RNA-dependent RNA polymerase, amnion epithelial cells and their exosomes. At the same time, the potential use of mesenchymal stem cells in patients with severe COVID-19 pneumonia is reviewed. Difficulties and questions regarding the use of the above therapeutic methods in pregnant women are highlighted. Aspects of the use of surfactant preparations in newborns at risk of new coronavirus infection are considered.

To conduct a study of the quality of life of children who have suffered from multisystem inflammatory syndrome (MIS‐C) associated with SARSCoV‐2 in the post‐rehabilitation period against the background of correction of microecological imbalance.The study involved 49 children aged 2 to 12 years who underwent MIS‐C associated with SARS‐CoV‐2 and received treatment in a hospital (DGKB No. 3 in Novosibirsk), and then underwent rehabilitation on an outpatient basis. The duration of rehabilitation was 7–8 weeks. All children were prescribed a course of additional rehabilitation for 30 days in order to correct microecological imbalance, which included: Biovestin, a dietary supplement in liquid form, containing bifidobacteria of the Bifidobacterium longum MC‐42 strain; the official drug, Kudesan, (active ingredient Coenzyme Q10); and the official drug, Succinic Acid. The assessment of physical, social, educational, emotional and psychological functioning, as well as quality of life as an integrating indicator before and after a comprehensive rehabilitation course using the parental form of the Reds OL Generic Core Scales questionnaire (Russian version) was carried out.After the rehabilitation course, children who underwent MIS‐C associated with SARS‐CoV‐2 showed signs of dysfunction of various organs and systems, which may be the result of an imbalance in the microbial ecosystem and requires mandatory correction. The introduction of a probiotic product and drugs affecting metabolic processes into the rehabilitation course led to a decrease in inflammatory reactions, as well as normalisation of metabolic processes and increased oxygenation, which improved the condition of the children and their quality of life.Federal Research Center for Fundamental and Translational Medicine (FRC FTM), Siberian Branch, Russian Academy of Sciences

The presence of infectious inflammatory process in a pregnant woman can lead to a disorder in the “mother – placenta – fetus” system.Aim of the study was to investigate the level of regulatory and pro-inflammatory molecules in pregnancy occurring against the background of chronic pyelonephritis without exacerbation.Material and methods. The concentration of IL-17A, monocytic chemotactic protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and IgG autoantibodies to double-stranded DNA (AAT to nDNA) was determined in the blood serum of pregnant women with a gestation period of 36–40 weeks using ELISA.Results. It has been shown that in the third trimester of pregnancy occurring against the background of chronic pyelonephritis without exacerbation, compared with a normal pregnancy, the level of MHP-1 and IL-17A increases, the content of VEGF decreases, and the concentration of AAT to nDNA does not change significantly. An increase in the proinflammatory cytokine IL17A and a decrease in VEGF level can lead to intrauterine fetal growth retardation due to inhibition of amino acid transporters in the placenta.Conclusions. In pregnancy occurring against the background of chronic pyelonephritis without exacerbation, a change in the level of IL17A, MСP-1, VEGF can have a significant impact on the course of pregnancy.

The article presents data of the influence of cytokines of different directions of glucose and lipid metabolism in obesity. A change of the basic paradigm regarding adipose tissue has contributed to a number of recent discoveries. This concerns such basic concepts as healthy and diseased adipocytes, and, as a consequence, changes of their metabolism under the influence of cytokins. Distinguishing the concept of organokines demonstrates that despite the common features of cytokine regulation, each organ has its own specifics features of cytokine regulation, each organ has its own specific an important section of this concept is the idea of the heterogeneity of adipose tissue. Knowledge of the function of adipose tissue localized in different compartments of the body is expanding. There are date about the possibility of transition of one type of adipose tissue to another. A possible mechanism linking adipose tissue inflammation and the formation of insulin resistance (IR) is presented in this paper. The mechanism of IR development is closely connected with to proinflammatory cytokins disordering the insulin signal, accompanied by a decrease of the work of glucose transporters. A decrease of the income of glucose into cells leads to a change of glycolysis level to an increase of the fatty acids oxidation. Cytokins are able to participate in the process of the collaboration of some cells with others, that occurs both during physiological and pathological process.

Multisystem inflammatory syndrome (MIS-C) is a new childhood disease associated with coronavirus SARS-CoV-2 that manifests itself 3–4 weeks after infection. The development of MIS-C is possible, despite the asymptomatic course of coronavirus infection. The pathogenetic features of MIS-C remain unclear. The aim of the study was to investigate the state of peripheral blood parameters in children with multisystem inflammatory syndrome associated with SARS-CoV-2 upon admission to a hospital. Material and methods. We examined 52 children with MIS-C from 1 to 14 years old, hospitalized in Children`s Clinical Hospital No. 3 in Novosibirsk in October–December 2020. Testing for the isolation of SARS-CoV-2 RNA in scrapings from the nasopharynx and oropharynx was carried out using real time PCR (test systems of DNA-Technology, Russia). The presence of specific IgM and IgG antibodies to SARS-CoV-2 in blood serum was determined by ELISA using Vector-Best kits (Russia). Results and discussion. It was noted that SARS-CoV-2 virus RNA was found only in 12.8 % of cases, while specific IgG antibodies in blood serum were detected in 100 % of children. IgM to SARS-CoV-2 antigens were detected in the blood serum only in 53.85 % of children with MIS-C. It has been established that unexpressed leukocytosis was found both in children under the age of 7 and in children of 8–14 years old. However, the leukocytes content in children of the older age group was significantly lower than in children aged 1–7 years. At the same time, in both age groups, some children had extremely low values of the indicator. The causes of severe leukopenia against the background of excessive inflammation remain unclear. Age groups (1–7 and 8–14 years) do not differ statistically significantly in the relative content of lymphocytes and neutrophils. In the study of individual values of the relative content of lymphocytes within the age groups, it was noted that only some children had lymphopenia of varying severity. Conclusions. Against the background of minor leukocytosis in children with MIS-C, upon admission to the hospital, there is a tendency to develop both relative and absolute lymphopenia, regardless of age. The study noted an extremely pronounced variability of individual values of the evaluated peripheral blood parameters, regardless of age, which, with similar clinical symptoms, characterized as MIS-C, requires further study in dynamics, taking into account the initial values of the indicators.There is no pronounced relationship between the leukocytes content and specific IgM antibodies to SARS-CoV-2 antigens in the blood.

The issues of immunopathogenesis of acute respiratory viral infections (ARVI) remain relevant, despite a long history of study. The aim of the study was to investigate the characteristics of the content of some cytokines in the blood serum of children with ARVI caused by DNA and RNA-containing viruses. Material and methods. We examined 92 children with ARVI at the age from 1 to 15 years, hospitalized in the hospital of the Children’s Clinical Hospital No. 6 (Novosibirsk). In order to determine the etiological factor, a study was carried out using the RT-PCR method (test systems AmpliSensORVI-screen-FL, “InterLabService”, Russia) of mucus from the nose and throat for the presence of genetic material of viruses that cause ARVI. Determination of the content of IL-8, IL-17, IFN-γ in the blood serum in children of all groups was carried out by the method of solid-phase ELISA using commercial test systems of LLC “Cytokin” (Russia). Results and discussion. 4 groups were formed: group I (n = 20) children with ARVI caused by DNA-containing viruses (group B, C, E adenoviruses, bocaviruses); group II (n = 53) children with ARVI caused by RNA viruses (RS virus, metapneumovirus, parainfluenza viruses 1, 2, 3, 4, rhinovirus and coronoviruses); group III (n = 12) children with ARVI caused by mixed infection; group IV (n = 7) – the genetic material of the pathogen has not been isolated. Concentration of IL-8, IL-17, IFN-γ was significantly increased in all groups compared to the normative values. Higher values of IFN-γ and IL-8 were revealed in patients with DNA viruses compared with the group with RNA-containing viruses, although the excess of IFN-γ was not statistically significant. Differences in the content of IFN-γ, IL-8 and IL-17 were noted for various etiological viral agents, but they were not significant. Conclusions. The results obtained can serve as confirmation that the functional characteristics of the response of the immune system in children with ARVI are determined not so much by the etiological factor as by its individual state. With ARVI in children, the presence of genetic material from more than one virus, apparently, is not a significant potentiating factor in the activation of the immune response. At the same time, a negative PCR result with a detailed clinical picture of ARVI does not exclude the viral genesis of the disease.

Aim. To determine the presence or absence of specific IgG antibodies against SARS-CoV-2 antigens in outpatient clinic staff and to compare clinical and immunological features from April to August 2020.Materials and Methods. The control group comprised 386 employees of the Novosibirsk City Clinical Polyclinic №13.The determination of IgG antibodies against SARS-CoV-2 antigens in blood serum was performed by using the ELISA method. A real time method of reverse transcription and polymerase chain reaction was used to extract RNA SARS-CoV-2 from nasopharyngeal and oropharyngeal swabs.Results. Specific IgG antibodies against SARS-CoV-2 antigens were detected in 32 (8.42%) employees of the polyclinic. Antibodies were not detected in 91.58% of employees. 9 members (28.12%) had clinical symptoms of varying degrees of disease severity in the group of employees with the presence of antibodies, 4 members of this group (12,51%) had bilateral community-acquired pneumonia with signs of COVID infection, another 5 members (15.61%) with antibodies had signs of ARVI of mild and moderate severity. RNA SARS-CoV-2 in the group of employees with the presence of antibodies and clinical implications was not detected in any case; 23 (71.88%) members with the presence of IgG-antibodies did not have clinical implications of the disease.Conclusion. The presence of specific antibodies against SARS-CoV-2 in employees with clinical implications of COVID-19 without detection of the RNA virus in the biological material is a retrospective confirmation of the etiology of the transferred infection. The detection of specific antibodies in persons who did not have clinical implications can serve as confirmation of the asymptomatic course of the transferred coronavirus infection.

The purpose of the study was to examine the characteristics of the content of cytokines in the peritoneal fluid in women of reproductive age with infertility against the background of chronic inflammatory diseases of the pelvic organs in the stage of clinical remission.Material and methods. A study was conducted of 50 patients aged 23-36 years with a verified diagnosis of infertility of tubal peritoneal genesis against a background of chronic inflammatory diseases of the reproductive sphere in the stage of clinical remission. As a control group, 15 practically healthy women aged 25-37 years were examined. Concentration of cytokines TNF-a, IL-4, IL-6, IL-10, IFN-y, MCP-1 in the peritoneal fluid was measured by enzyme-linked immunosorbent assay.Results and discussion. In the main group of patients with tubal-peritoneal infertility, the activity of local inflammatory reactions is tested in the period of clinical remission of a chronic inflammatory process. This is confirmed by a significantly higher level of TNF-a, IL-4, IL-6, IFN-y, MCP-1 in the peritoneal fluid compared to the control group. The studied biologically active substances play a significant role in the development of the immune response, as well as fibroplastic processes. The results can be regarded as the latent development of the immune response in reactions to constant antigenic stimulation from the focus of chronic inflammation, which is a significant factor in the development of adhesions in the formation of infertility, and requires the inclusion of immunotropic therapy methods in treatment.

Purpose. To study the content of cytokines and growth factors in the intraocular fluid of patients with developed stage of primary open-angle glaucoma (POAG).Materials and methods. 56 patients with a verified diagnosis developed stage of primary open-angle glaucomawere examined. The control group consisted of 30 patients with a diagnosis of uncomplicated cataract. A concentration of 17 cytokinesand 3 isoforms of the transforming growth factor (TGF) β was determined using a Bio-Plex Pro™ Human Cytokine 17-plex Assay and Bio-Plex Pro™ and TGFβ 3-plex Assay kit by flow-through fluorometry on a Bio-Plex 200, Bio-Rad double beam laser analyzer, USA.Results. Astatistically significant increase was shown in the concentrations of cytokines and growth factors (interleukins (IL) 4, 6, 7, 8, 12, 17, TGFβ 1, 2, 3, macrophage inflammatory protein 1 β) in the intraocular fluid of patients with developed stage of the primary open-angle glaucoma in respect to data obtained from the study of the intraocular fluid of the persons with uncomplicated cataract, as well as a statistically significant decrease in the concentrations IL-2, IL-10, granulocyte-macrophage colony-stimulating factor.Conclusion. In the pathogenesis of primary open-angle glaucoma, the activity of the local chronic inflammatory process is determined. This is confirmed by statistically significant changes in the studied cytokines and growth factors. Increase in the concentrations of the studied representatives of the superfamily of transforming growth factors-beta, which have anti-inflammatory activity, the ability to stimulate proliferation, cell growth, synthesis of extracellular matrix proteins, etc., attests to their importance in the mechanisms of primary open-angle glaucoma development. Increase concentrations of IL-7 in the intraocular fluid of patients with primary open-angle glaucoma allows us to assume participation in the pathogenesis of the primary open-angle glaucoma of this autocrine mediator of activation of the growth of lymphatic structures.

Purpose: to study the activity of the local inflammatory process in patients with complicated cataracts with pseudoexfoliation syndrome before and after phacoemulsification with the primary posterior capsulorhexis. 54 patients (54 eyes) aged 50 to 92 years (76 ± 7.43) appealed for surgical treatment of complicated cataracts with pseudoexfoliation syndrome were examined. The concentration of IL-6, IL-10, MMP-9, TGF-β1 was determined in the tear fluid of patients before and on the 5th day of the postoperative period. It was established that the activity of local inflammatory process (high concentrations of IL-6 and MMP-9) is determined in patients with complicated cataracts with pseudoexfoliation syndrome. The identified increase in TGF-1 concentrations is a significant factor in the formation of the pseudoexfoliation material. It has been established that the use of a modified surgical technique in patients with pseudoexfoliation syndrome does not lead to activation of the local inflammation process

Purpose: to study the content of proinflammatory cytokines IL-6, IL-8 and IL-17 in lacrimal and intraocular fluid in patients with advanced stage of primary open-angle glaucoma. Material and methods. The study included 56 patients with advanced stage diagnosis of primary open-angle glaucoma (POAG). The diagnosis was determined by ophthalmological examination, including visual acuity, binocular ophthalmoscopy, spheroperimetry, echoophthalmography, optical coherence tomography, intraocular pressure measurement. The number of men was 21 (37.5 %), women - 35 (62.5 %), the average age of patients was 62.8 ± 4.3 years. Exclusion criteria were acute and exacerbation of chronic inflammatory diseases of the organ of vision, diabetic retinopathy, neovascular glaucoma, uveitis, hemophthalmia, autoimmune and tumor processes of any localization, as well as acute and exacerbations of chronic inflammatory diseases of any organs and systems. Patients who took drugs containing prostaglandins analogues for intraocular pressure normalization, that could activate the inflammatory process, were excluded from the study. A comparison group was composed of 30 patients with the uncomplicated cataract diagnosis. All patients underwent the determination of IL-6, IL-8, IL-17 in the lacrimal and intraocular fluid. Results. It has been established that the significant increase in the concentrations of IL-6, IL-8 and IL-17A in the lacrimal and intraocular fluid was revealed in patients with advanced stage of POAG in comparison with those obtained in patients with uncomplicated cataracts. The obtained data testify to the presence of local destructive-inflammatory process in the mechanisms of the development of primary open-angle glaucoma. The revealed unidirectional change in the concentrations of IL-6 (2.8 times the lacrimal fluid and 5.2 times in the intraocular fluid), IL-8 (1.5 times in the lacrimal fluid and 4 times in the aqueous humor), IL-17 (1.75 times in lacrimal fluid and 1.95 times in the intraocular fluid) allows us to conclude that lacrimal fluid can be used to assess changes in cytokine content in the pathogenesis of ophthalmic diseases.

Abstract. Patients with exacerbation of chronic herpesvirus infection were subjected to immunocorrection therapy. In the course of treatment, time-dependent correlations were found between the changes in production of IFNγ, IL-1β and IL-6, and initial level of IFNγ. The patients with high initial concentrations of IFNγ did also exhibit above-normal initial IL-1Β and IL-6 values, as compared to appropriate parameters for a sub-group with low IFNγ levels. In the course of immunocorrection with Echinacea, all the patients showed increase in IFNγ levels. However, due to initially low IFNγ values, its increase was more pronounced than in persons with high background levels of IFNγ. Dynamics of IL-1Β decrease and changes in IL-6 concentrations were more expressed in cases of higher initial levels of these cytokines. The alterations revealed for IFNγ, IL-1Β and IL-6 levels confirm that immunocorrection with Echinacea causes reduced intensity of inflammation and activation of antiviral immune response. (Med. Immunol., 2008, vol. 10, N 2-3, pp 283-290).

Abstract. In present work, we studied some interrelations between tobacco smoking and the processes of immune system stimulation in healthy blood donors. In our opinion, this issue is especially important for the big industrial center, with rather strong antigenic exposure of the organism. The levels of circulating immune complexes (CIC) were used as a marker index which reflects specific antigen-antibody interactions during inflammation. According to the results obtained, the majority of persons who have high CIC levels were tobacco smokers (53.76%). Moreover, the percentage of persons with high CIC content, like as the mean values of this index is increased proportionally to the duration of smoking. A mixture of tobacco smoke components seems to exert direct toxic effect upon various compartments of the immune system and causes local irritation of bronchial tree, thus producing local and systemic inflammatory reaction. It is, possibly, an additional factor which determines activation of immune system, with a background of adverse antropogenic exposures typical to industrial centers. The data obtained allow us to affirm a toxic action of tobacco smoke upon the organism of smokers, with development of inflammatory reactions that are displayed as increased CIC levels at preclinical stage.