Galina A. Skosyreva

BACKGROUND: The problem of the pathogenesis of the multisystem inflammatory syndrome (MIS-C), associated with SARS-CoV-2, remains relevant, but is still far from being resolved. In this regard. AIM: The aim our research was to study and evaluate the levels of autoantibodies to native and denatured DNA in the blood serum of children who underwent MIS-C, associated with SARS-CoV-2, in comparison with the initial period of the pathological process. MATERIALS AND METHODS: 101 children aged 2 to 17 years old were examined, 77 of them was with a confirmed diagnosis of MIS-C associated with SARS-CoV-2. We have formed 3 groups: group 1 — children with MIS-C upon admission to the hospital; group 2 — children who underwent MIS-C after a course of rehabilitation; group 3 — comparison group. All children underwent determination of the concentrations of IgG-autoantibodies to native and denatured DNA in blood serum, which was performed by EIA ELISA using commercial test systems of Vector-Best LLC (Russia) according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using the Statistica v. 10.0 application package. Statistical processing used the Newman–Keuls multiple comparison test. RESULTS: It was noted that both in the initial period of MIS-C and after rehabilitation, an increased content of autoantibodies to nDNA and dDNA was determined compared to the control group. At the same time, there was a significant excess of the levels of indicators in the post-rehabilitation period compared with the initial period of MIS-C. During a clinical examination of children who underwent MIS-C, most of them noted the appearance of pain in the joints. The results obtained indicate the persistence of inflammatory reactions with the development of an autoreactive component. This requires both the search for risk markers for the development of MIS-C and further monitoring of children who have undergone MIS-C to prevent autoimmune complications, including arthritis, damage to the vascular endothelium with the possible formation of thrombotic complications. CONCLUSIONS: In the acute period of MIS-C and after rehabilitation, increased levels of the average content of autoantibodies to nDNA and dDNA were noted compared to the control. Individual values of autoantibodies to nDNA and dDNA exceeded normative levels of the indicator were found in a significantly larger number of children in the post-rehabilitation period after MIS-C, and this excess was more pronounced compared to the acute period of the process. When assessing the clinical condition of children after MIS-C, most of them showed pain in the joints during exercise, abdominal and neurological disorders, and decreased tolerance to physical activity, which indicates persistent inflammatory reactions.

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.

Содержание цитокинов в сыворотке крови детей, перенесших мультисистемный воспалительный синдром, связанный с SARS-CoV-2

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.

Особенности иммунного реагирования у детей при острых респираторных инфекциях, вызванных ДНК- и РНК- содержащими вирусами

The relevance of research on a novel coronavirus infection is associated with an increase in the incidence among children since 2021, which may be due to the accumulation of mutations in the virus genome and its evolution towards increased contagiousness, replicative ability, and evasion of immune protection. While there are many studies in adults, data analyzing the clinical course of the disease in pediatric patients infected with SARS-CoV-2 are limited, particularly regarding adolescents. Objective. To study the clinical and laboratory features of the course of a novel coronavirus infection in hospitalized adolescents in Novosibirsk during the first, second and third waves of the pandemic. Мaterials and methods. A retrospective analysis of case histories of 125 children treated at Novosibirsk Children's Clinical Hospital No 6 with a confirmed diagnosis of coronavirus infection during three pandemic waves was carried out (June–August 2020, October–December 2020, June–August 2021). Based on these time intervals, three groups of adolescents admitted to the hospital during the first, second, and third waves of coronavirus infection were formed. SARS-CoV-2 RNA in nasopharyngeal and oropharyngeal scrapings was determined using the PCR-RT method. Biochemical and general clinical studies were performed in accordance with the guidelines of the Ministry of Health of the Russian Federation. Statistical processing was carried out using the Satistika 7.0 software package (StatSoft, USA). Differences between the groups were assessed using the Z-test and the Mann–Whitney U test. Differences between the compared series were considered statistically significant with a probability level of 95%. Results. It was shown that during three pandemic waves (June 2020 – August 2021), more than half of the hospitalized children were adolescents. At the same time, regardless of the pandemic wave, intoxication, catarrhal and intestinal syndromes predominated in hospitalized adolescents. CNS injury symptoms were significantly less frequent in the first wave, as were skin rashes. Cough in the third wave was observed in 100% of hospitalized adolescents. The average values of the parameters of complete blood count, as well as CRP, D-dimer and ferritin had no statistically significant differences in different pandemic waves, but there was a significant variation in individual values within the groups in each wave. Key words: adolescents, coronavirus infection, COVID-19, clinical manifestations, laboratory parameters

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.