The aim of the research is to study of the efficacy and safety of VIFERON® drug, rectal suppositories (interferon α-2b) 1,000,000 IU and 3,000,000 IU, and VIFERON®, gel for external and local use (interferon α-2b) 36,000 IU/g , in the complex therapy of a сoronavirus disease 2019 (COVID-19) in children. Materials and methods of research: as part of the open multicenter prospective controlled non-randomized study, 140 patients aged 1 to 17 years with the сoronavirus disease 2019 (COVID-19) were examined, and hospitalized in the infectious diseases hospital (Krasnoyarsk interdistrict clinical hospital № 1) in Krasnoyarsk from 20.04.20 to 1.08.20. Depending on the conducted antiviral therapy, the observed patients were divided into 2 groups: the main (70 people) and control (70 people). Starting from the moment of hospitalization, the main group of patients in the complex therapy received the preparation of interferon (IFN) α-2b with antioxidants (vit E and C), rectal suppositories, and IFNα-2b, gel for external and local use, according to the proposed schemes depending on age; patients of the control group were prescribed Umifenovir (Arbidol®) in age-specific dosages. The criteria of effectiveness of the therapy were the period of treatment of the main clinical symptoms of the disease (cough, nasal congestion, runny nose, sore throat, conjunctivitis, taste and smell impairment, abdominal pain, diarrhea, etc.), elimination of viral antigen in samples from the nasopharynx and feces, product dynamics of IgM and IgG antibodies to SARS-CoV-2 in the blood serum. Results: the clinical efficacy and safety of high dose polytherapy of IFNα-2b with antioxidants, rectal suppositories in combination with IFNα-2b with antioxidants, gel for external and local use in the therapy of COVID-19 in children were confirmed. Since the appointment of therapy in patients of the main group, in comparison with the control group, the time for relief of the main clinical symptoms of COVID-19 has been statistically significantly reduced: nasal congestion – from 7 to 3 days (p=0,0001), sore throat – from 7 to 3 days (p=0,0001), hyperemia in the oropharynx – from 10 to 5 days (p=0,0001), mild cough – from 7 to 5 days (p=0,05), catarrhal conjunctivitis – from 5 to 3 days (p=0,012), smell disorders – from 10 to 4 days (p=0,001) and taste – from 10 to 4 days (p=0,001). The period of complete relief of all clinical symptoms according to the «total score» was statistically significantly reduced from 9 days in the control group to 5 days in the main group (p=0,05). The elimination time of SARS-CoV-2 from the nasopharynx was also statistically significantly reduced by 5 days in the main group of patients (p=0,05). In patients receiving increased doses of IFNα-2b with antioxidants, intestinal sanitation occurred 2,5 times more frequent, statistically significant increase in the level of IgG antibodies to SARS-CoV-2 was detected in comparison with patients of the control group (p=0,05). No adverse events were recorded in the observed patients of both groups. Conclusion: the proven efficacy and safety of combined antiviral therapy with IFNα-2b with antioxidants, rectal suppositories in combination with IFNα-2b with antioxidants, gel for external and local use, are the basis for its widespread implementation into pediatric practice for the treatment of patients with сoronavirus disease 2019 COVID-19.
The aim of the study was to investigate the features of changes in the subset composition of monocytes and their phagocytic activity in children with infectious mononucleosis (IM) under the influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. We examined 84 children aged 3 to 11 years with Epstein-Barr virus (EBV) infection. EBV infection was diagnosed on the basis of clinical signs of IM, a positive test for EBV DNA in blood lymphocytes and results of ELISA tests (EBV-VCAIgM (+), EBV-EA-DIgG (+)). The control group consisted of 40 practically healthy children of the same age range. Monocytes were obtained by the standard method of adhesion to plastic from mononuclear cells isolated from heparinized venous blood by density gradient centrifugation. The isolated monocytes were divided into two samples: control (without GM-CSF) and experimental (50 ng of GM-CSF per 1 ml of cell suspension). The subset composition and phagocytic activity of monocytes in both samples were determined by flow cytometry after incubation for 1 hour at 37C in a CO2-incubator. It was found that in children against the background of the development of IM, the subpopulation composition of monocytes in the blood changes and their phagocytic activity is impaired. It was found that the subset composition and phagocytic activity of the blood monocytes changed in children against the background of the development of IM. Changes in the subset composition of monocytes against the background of acute IM did not depend on the age group of children (3-6 and 7-11 years) and were characterized by an increase in the number of pro-inflammatory (intermediate) monocytes and a decrease in the content of anti-inflammatory (non-classical) monocytes. Features of violation of the phagocytic activity of the monocytes in children with IM depended on age. The phagocytic activity of all three subsets of the monocytes was reduced in children with IM 3-6 years old while children with IM 7-11 years old had reduced phagocytic activity only of intermediate and non-classical monocytes. The effect of GM-CSF in vitro on monocytes in patients with IM, regardless of the age of children, led to a significant increase in the level of anti-inflammatory monocytes while the phagocytic activity of cells changed less. An increase in the phagocytic number for classical monocytes after incubation with GM-CSF in vitro was noted in children with IM at the age of 3-6 years while the phagocytic index of this fraction of monocytes remained unchanged. The level of the phagocytic index increased only in classical monocytes of children with IM aged 7-11 years. The presented results determine the scientific and clinical value of studying the mechanisms of the effect of GM-CSF on cells of the immune system and prove that this cytokine can be used in a new immunotherapeutic strategy for the treatment of IM.
9114. Starodubov V.I., Rudnev S.G., Nikolaev D.
Objective. To analyze the production of active oxygen species (AOS) by peripheral blood neutrophils in children with infectious mononucleosis (IM) after their exposure to granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. Patients and methods. We examined 78 children aged 3 to 11 years in the acute period of IM (including 47 children aged 3–6 years and 31 children aged 7–11 years). The control group comprised 40 healthy children matched for age. Luminoldependent chemiluminescence (CL) of peripheral blood neutrophils was assessed using the method of De Sole et al. The following CL parameters were measured: time to reach the maximum (Tmax), maximum value (Imax), and the area (S) under the chemiluminescent curve. Results. Children with IM (from both age groups) demonstrated lower spontaneous lucigenin-dependent chemiluminescence of neutrophils than controls: Tmax (p < 0.001 and p = 0.036, respectively), Imax (p = 0.024 and p = 0.025), and S (p = 0.01). Incubation of neutrophils with GM-CSF caused changes in luminol-dependent chemiluminescence only in children with MI from both age groups: Tmax decreased, whereas Imax and S increased. IM patients aged 7–11 years were found to have higher levels of chemiluminescence of neutrophils exposed to GM-CSF in vitro than IM patients aged 3–6 years (Tmax (p < 0.001) and SGM-CSF/Ssp. (p = 0.024)). Conclusion. Our findings suggest that GM-CSF can increase functional activity of neutrophils. This might facilitate adaptive immunity at periphery. Key words: infectious mononucleosis, neutrophilic granulocytes, chemiluminescence of neutrophils, granulocyte-macrophage colony stimulating factor
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