Early Convalescent Period Research Articles

T Regulatory Cell Subsets Do Not Restore for One Year After Acute COVID-19.

COVID-19, caused by SARS-CoV-2, triggers a complex immune response, with T regulatory cells (Tregs) playing a crucial role in maintaining immune homeostasis and preventing excessive inflammation. The current study investigates the function of T regulatory cells during COVID-19 infection and the subsequent recovery period, emphasizing their impact on immune regulation and inflammation control. We conducted a comprehensive analysis of Treg subpopulations in peripheral blood samples from COVID-19 patients at different stages: acute infection, early convalescence, and long-term recovery. Flow cytometry was employed to quantify Tregs including "naïve", central memory (CM), effector memory (EM), and terminally differentiated CD45RA+ effector cells (TEMRA). Additionally, the functional state of the Tregs was assessed by the expression of purinergic signaling molecules (CD39, CD73). Cytokine profiles were assessed through multiplex analysis. Our findings indicate a significant decrease in the number of Tregs during the acute phase of COVID-19, which correlates with heightened inflammatory markers and increased disease severity. Specifically, we found a decrease in the relative numbers of "naïve" and an increase in EM Tregs, as well as a decrease in the absolute numbers of "naïve" and CM Tregs. During the early convalescent period, the absolute counts of all Treg populations tended to increase, accompanied by a reduction in pro-inflammatory cytokines. Despite this, one year after recovery, the decreased subpopulations of regulatory T cells had not yet reached the levels observed in healthy donors. Finally, we observed the re-establishment of CD39 expression in all Treg subsets; however, there was no change in CD73 expression among Tregs. Understanding these immunological changes across different T regulatory subsets and adenosine signaling pathways offers important insights into the disease's pathogenesis and provides a broader view of immune system dynamics during recovery.

The effect of a new coronavirus infection on hemogram parameters in the early convalescence period of patients with coronary heart disease

Laboratory data, especially a general blood test, play an important role in the treatment of infectious diseases, including COVID-19. However, in patients with coronary heart disease (CHD) and COVID-19, a general blood test is rarely analyzed and is insufficient to fully assess an impact of the new coronavirus infection on patients with cardiac diseases. The aim of the study was to analyze a COVID-19 effect on hemogram parameters in the early recovery period of patients with coronary heart disease. The study was performed at the Kursk City Clinical Hospital for Emergency Medical Care in the years 2021–2022, which involved 58 mature-aged patients (45–59 years old) suffering from coronary heart disease who had a new coronavirus infection and 62 elderly patients suffering from coronary heart disease alone. Morning blood sampling was carried out from the forearm superficial veins into Vacutainer test tubes added with a coagulation activator. In elderly patients, 3–4 weeks after recovery, significant changes in red blood parameters persisted — a decline in the level of peripheral blood erythrocytes, hemoglobin and hematocrit. Elderly patients with coronary heart disease comorbid with a moderate new coronavirus infection, 3–4 weeks later had also higher count of leukocytes, neutrophils, segmented neutrophils and ESR level relative to comparison group. It should be noted that in the early convalescence period elderly patients with coronary heart disease and COVID-19 had significantly elevated ESR, which confirms ongoing sustained inflammatory process. After evaluating the information content according to the calculated Kullback informativeness assessment for analyzed general blood test parameters, it was found to peak for platelet and leukocyte counts as well as ESR level. Thus, among the analyzed indicators in the general blood test, it turned out that platelet and leukocyte count along with ESR level were most informative and of prognostic significance during early convalescent period of elderly patients with coronary heart disease comorbid with a new coronavirus infection, which are proposed to be used as biomarkers of early convalescent period.

The influence of the Epstein-Barr virus on paraclinical indicators and cytokine levels in children with rotavirus gastroenteritis

The aim. To identify the influence of the latent form of Epstein-Barr virus infection on the clinical picture, parameters of clinical blood analysis and cytokine response of children with rotavirus gastroenteritis.
 Materials and methods. 56 children were examined. Of them, 33 children (group 1) had no background infection with herpesviruses, and 23 patients (group 2) suffered from rotavirus gastroenteritis against the background of Epstein-Barr virus (EBV) infection. The patients were comparable in terms of sex, age and disease severity. Differences at p <0.05 were considered statistically significant.
 Results. The analysis of the obtained data showed that the latent form of EBV infection affects the clinical picture, indicators of clinical blood analysis and the reaction of serum cytokines of children with rotavirus gastroenteritis.
 Сonclusions. A comparative analysis revealed that a latent form of herpesvirus infection in children with rotavirus gastroenteritis is associated with lower temperature reaction and a lower frequency of vomiting in the acute period of the disease against the background of longer persistence of fever, diarrhoea and catarrhal syndromes. On the part of the investigated laboratory indicators, the presence of EBV infection is characterized by a lower level of haemoglobin (р = 0,013) against a higher content of neutrophils (p = 0.002), eosinophils (p = 0.033) and monocytes (p < 0.001) in the acute period of RVI, and a significantly higher content of eosinophils (p = 0.001) and monocytes (p < 0.001) against the background of a lower level of the relative content of lymphocytes compared to patients of Group 1 in the period of early convalescence. Changes in the cytokine response in children with mixed infection are characterized by a significantly lower concentration of IL-1β at the onset of RVI and a higher content of IL-4 and TNF-α throughout the disease compared to children with mono-RVI

Патогенетические связи цитокинового и оксидативного статусов пациентов с клещевым риккетсиозом, обусловленным R. heilongjiangensis

The purpose — to determine pathogenetic connections between the level of pro-inflammatory immunocytokines and oxidative stress indicators in the systemic blood circulation in patients with tick-borne rickettsiosis. Material and methods. The levels of some interleukins and indicators of the oxidant-prooxidant system in patients with a moderate form of tick-borne rickettsiosis caused by R. heilongjiangensis were researched and analyzed. Results. At the height of the disease, we found a statistically significant increase (p < 0.01) in the blood serum of all pro-inflammatory cytokines studied (IL-6, IL-8, TNF), combined with a significantly pronounced activation of free radical oxidation processes (p ˂ 0.0002). During the early convalescence period, there was a decrease in the level of IL-6 and TNF by 7 and 2.6 times, respectively (p < 0.0001), while the level of IL-8 statistically significantly increased twofold by the time of discharge relative to the height of the disease (p < 0.05). In the same period, oxidative stress indicators increased statistically significantly (p ˂ 0.0001) compared to the acute period: Ssp — 6 times; h — 1.3 times; Sind-1 — 1.3 times; Slum — 1.4 times; Sind-2 — 1.3 times. A correlation analysis revealed a significant direct relation between the content of the studied interleukins and chemiluminescence indices in the blood serum. Conclusion. Changes in cytokine status identified during the study in patients with tick-borne rickettsiosis caused by R heilongjiangensis, indicate the participation of interleukins in the disease pathogenesis. The increase in the level of reactive oxygen species during early convalescence may indicate that clinical recovery does not reflect the pathogenetic completion of the infection. The revealed correlation between indicators of cytokine and oxidative status testifies to their joint participation in the pathogenesis of tick-borne rickettsiosis caused by R. heilongjiangensis.

Rhinocerebral Form of Invasive Mycosis in COVID-19 Patients: Clinical Course, Diagnosis, Treatment Experience

Background. The incidence of invasive mycoses is reported to increase among patients with a history of new coronavirus infection COVID-19. Adhesion and damage of endothelial cells by zygomycetes lead to fungus angioinvasion, release of a large number of fungal proteases, lipases and mycotoxins, as well as vascular thrombosis, subsequent necrosis of tissues.Objectives. Improvement of the diagnosis and treatment for COVID-19 associated invasive mycosis.Methods. Examination and treatment of 143 patients with invasive mycosis of the maxillofacial area in the period from August 2021 to May 2022 at the Maxillofacial Unit of Regional Clinical Hospital of Emergency Medical Care, Krasnodar Krai, Russia. The diagnosis was confi rmed by cytological, culture-based methods, as well as pathomorphological study of surgical specimen. Follow-up monitoring was carried out in 1, 3, 6 months, with repeated CT and MRI investigations. The group under follow-up monitoring included 91 patients. The incidence of signs was determined via descriptive statistics methods in proportion of the total number of observations and expressed as a percentage. Statistika 12.5 and Excel 2010 (Windows 10) were used in the study, the graphical representation of the material was made in the same programs.Results. Manifestation of invasive mycoses of the maxillofacial area occurred during the early convalescent period of coronavirus infection in specialized infectious hospitals or within two weeks after discharge from the hospital. A typical clinical picture includes rhinocerebral zygomycosis with the development of fungal osteomyelitis of the upper jaw, nasal bones, zygomatic bone, ethmoidal labyrinth bones, sphenoid bone, frontal bone. 17 cases (11.9%) had a lethal outcome as a result of disseminated form of fungal infection caused by Mucorales (14 patients), Aspergillus (3 patients) with damage to the brain, lungs, kidneys and fatal massive necrotic lesions of the craniofacial area. An integrated approach embraced early antifungal therapy (Amphotericin B) as well as surgical debridement of the lesions and provided a positive effect in treatment.Conclusion. Invasive fungal infections require prompt diagnosis and early prescription of antifungal therapy (prior to histological confi rmation of diagnosis) to minimize consequences and prevent fatal outcome. Due to the nonspecifi c nature of clinical symptoms and diffi culties of early diagnosis of invasive zygomycosis and aspergillosis, it is necessary to be alert to potential invasive aggressive mycoses in immunocompromised patients who have a history of a new coronavirus infection COVID-19.

Biochemical markers of the severity and emergence of non-smooth progression of pseudotuberculosis in children

Background. Currently, pseudotuberculosis is characterized by a high incidence in children and it is the second acute intestinal infection by frequency after shigellosis. The search for relationships between early changes in cell metabolism, dysfunctions of some organs and body systems under the pathogenic effect of an infectious agent and the severity, the occurrence of a non-smooth course of pseudotuberculosis in children is relevant.
 Aim. Search for biochemical markers to predict the severity and occurrence of a non-smooth variant of the course of pseudotuberculosis in children.
 Material and methods. A prospective study was performed in 125 patients with pseudotuberculosis during periods of the disease height, early convalescence and recovery: 17 patients with mild severity and a smooth course of the disease; 64 with moderate severity and smooth course of the disease; 28 with moderate severity and non-smooth course, 16 with high severity and non-smooth course of the disease. The comparison group consisted of 45 children from the IIA health group. The distribution of the examined children by sex was equal, the age ranged from 9 to 13 years. The spectrophotometric method determined the following: in blood plasma the content of malondialdehyde; in erythrocytes the concentration of reduced glutathione, the activity of glutathione reductase, glutathione peroxidase, glutathione-S-transferase and catalase. The following ratios were calculated: reduced glutathione/malondialdehyde, reduced glutathione/glutathione reductase, reduced glutathione/glutathione peroxidase, reduced glutathione/glutathione S-transferase, glutathione peroxidase/catalase. Normality of the obtained data distribution was checked using the ShapiroWilk test, and the statistical hypotheses about the difference between the studied groups were checked using the nonparametric MannWhitney test at a significance level of p 0.05.
 Results. In the acute period of the disease, based on the analysis, a statistically significant decrease in the ratios of reduced glutathione/malonic dialdehyde, reduced glutathione/glutathione reductase, reduced glutathione/glutathione peroxidase by 3.0, 3.5 and 3.1 times, respectively, was established (p 0.05) in patients with mild severity and smooth course; 5.3, 5.1 and 3.8 times (p 0.05) with moderate severity and smooth course; 5.8, 4.0 and 3.0 times (p 0.05) with moderate severity and non-smooth course; by 8.1 and 6.1 times (p 0.05) with heavy severity and non-smooth course relative to control values. However, during the period of early convalescence of a non-smooth course, these indicators significantly decreased by 2.2, 4.4 and 1.8 times (p 0.05) in patients with moderate severity and by 3.4, 6.8 and 2.2 times ( p 0.05) with heavy severity relative to control values.
 Conclusion. Prognostically significant criteria for an increase in the severity and occurrence of a non-smooth course of pseudotuberculosis in children in the acute period of the disease are a decrease in the ratios of reduced glutathione/malonic dialdehyde less than 17.0, reduced glutathione/glutathione reductase below 38.0 and reduced glutathione/glutathione peroxidase less than 12.0.

Case series of acute kidney injury in children with SARS-CoV2 associated multisystem inflammatory syndrome

PurposeIn the first part of 2021 in Khimki regional hospital was eight-times increase of hemolytic-uremic syndrome (HUS) in children vs 2020. There are some data on association of HUS and COVID-19 in the literature. Our aim to describe case series of HUS in children with SARS-Cov2 associated multisystem inflammatory syndrome (MIS-C).Methods & MaterialsWe developed 8 children, age 1-11 yrs. (Me 4,5), 3M/5F. All had anemia (Hb 58 - 105, Me 83,8 g/l), thrombocytopenia (45 -136, Me 84*109/l) and kidney injury (azotemia, diuresis decrease, reduced GFR).ResultsIn anamnesis nobody had COVID-19, SARS-Cov2 RNA (oropharyngeal swab) was negative. 6 had anti-SARS-Cov2 IgG. 3 patients had antibody inversion during hospitalization. That means, they developed acute kidney injury (AKI) in early convalescence period of COVID-19. 6 children had fever, vomiting and diarrhea in anamnesis. 1 had only myalgia, 1 had transient hemorrhagic rush.All children had SIRS: ESR acceleration (15-43 mm/h), CRP increase in 6 cases (not more 5 norms), elevated ferritin (307-648 mkg/l) and D-dimer (3,24-8 mkg/ml). Mixed urinary syndrome was noted: proteinuria (0,1 - 6 g/l), hematuria (RBC 6-50). 100% had azotemia: urea (12,7-65,3, Me 35 mmol/l), creatinine (74-1450,2, Me 499 mkmol/l). GFR by Schwartz formula was reduced in all cases (1,7-58,1 ml/min/1,73 m2). 3 had anuria, 2 oliguria. Renal replacement therapy (RRT) performed in 5 cases: 3 hemodiafiltration (HDF) only; 2 - HDF + plasma exchange (1 - 7 procedures). All children were complex treated and discharged with normal clinical urine test and creatinine level, diuresis 1,6-2,4 ml/kg/h.ConclusionIn MIS-C pathogenesis thrombotic microangiopathia is one of the key points. We saw elevation of HUS in children in the COVID-19-pandemia period. 6 from 8 described cases had connection of AKI with previous COVID-19. In addition, they all had SIRS markers, corresponding diagnostic criteria of SARS-Cov2 associated multisystem inflammatory syndrome.

Иммунный статус детей, больных кишечными инфекциями, вызванными условно-патогенными микроорганизмами, на фоне инфицирования H.pylori

В статье показаны результаты изучения иммунного статуса детей, больных кишечными инфекциями, обусловленными условно-патогенными микроорганизмами, с фоновым инфицированием H.pylori. Доказано, что в острый период заболевания у больных с фоновым инфицированием H.pylori отмечается повышение уровня цитокинов и В-лимфоцитов, снижение содержания Т-лимфоцитов и факторов местного иммунитета, показатели иммуноглобулинов сохраняются в пределах физиологических. В периоде ранней реконвалесценции у больных отмечается незначительное повышение уровня Т-лимфоцитов, снижение уровня цитокинов, однако все показатели значительно отличаются от показателей здоровых детей; уровни иммуноглобулинов и факторов местного иммунитета остаются в пределах показателей острого периода. У больных с фоновым инфицированием H.pylori функционирование иммунной системы проходит в режиме гипокомпенсации. Эти данные теоретически обосновывают назначение иммунокорригирующей терапии этой группе больных. Учитывая более торпидную нормализацию показателей иммунитета больных на фоне инфицирования H.pylori, с целью объективизации оценки полноты выздоровления больных перед выпиской из стационара рекомендуется проводить исследование показателей иммунитета, и сохранение их изменений может быть использовано для обоснования расширения объема реабилитационных мероприятий на этапах диспансерного наблюдения за реконвалесцентами.

Integral leukocgram indices in children with coronavirus infection COVID-19

Objective. To study the changes in hematological leukocyte indices among children with coronavirus infection COVID-19 in the dynamics of infectious process.
 Materials and methods. The work is based on the analysis of clinical and laboratory data from 91 pediatric patients with COVID-19. On the basis of a general blood test, the following hematological leukocyte indices were determined: the entropy degree of leukogram according to A.V. Gorelov et al.; leukocyte intoxication index according to V.K. Ostrovsky; nuclear endotoxicosis degree index according to G.D. Dashtayants; Harkavi adaptation index; Krebs index; leukocyte index; neutrophils to monocytes ratio index; lymphocytes to monocytes ratio index.
 Results. The most sensitive hematological indices were the entropy degree of leukogram according to A.V. Gorelov et al., indicating a violation of the dynamic constancy of leukogram; neutrophils to monocytes ratio indices, lymphocytes to monocytes ratio indices, showing the presence of a viral infection. At the peak of the infectious process, C-reactive blood protein index significantly correlated with the endotoxicosis index according to G.D. Dashtayants (R = 0.271; p0.05), with neutrophils to monocytes ratio index (R = 0.276; p0.05); and in the period of early convalescence - with leukocyte intoxication index according to V.K. Ostrovsky (R = 0.743; p0.05), with endotoxicosis indices according to Dashtayants (R = 0.785; p0.05) and neutrophils to monocytes ratio index (R = 0.743; p0.05).
 Conclusions. The calculation of hematological leukocyte indices increases the information capability of the general blood test in children with coronavirus infection COVID-19, provides important additional information on intoxication syndrome, the state of immune response, the persistence of inflammatory process during the period of convalescence as well.

CLINICAL AND IMMUNOLOGICAL FEATURES OF ROTAVIRUS INFECTION IN CHILDREN INFECTED WITH EPSTEIN-BARR VIRUS.

The aim: To identify clinical and immunological features of acute rotavirus gastroenteritis occurring against the background of Epstein-Barr virus infection. Materials and methods: The study involved examination of 56 children. Of them, 33 children (1 group) did not have a background infection and 23 patients (2 group) suffered from rotavirus infection on the background of the latent form of Epstein-Barr virus infection. Children in these groups were compared by gender, age, severity of the disease and other parameters. Quantitative data were presented as mean and standard deviation (M±SD). Differences at p <0.05 were considered statistically significant. Results: The data suggest that the presence of background Epstein-Barr virus in children with rotavirus infection leads to later hospitalization, lower temperature response rates, lower frequency of vomiting at the onset of the disease, and longer duration of fever and diarrhea. At the same time, in children infected with Epstein-Barr virus, the relative content of CD8+ T lymphocytes dominated both in the acute period of the disease and in the period of convalescence against the background of reduced relative content of CD16+, CD22+ T lymphocytes and IgM in the period of early convalescence. Conclusions: The study allowed to reveal the influence of latent EBV infection on the clinical and immunological parameters of rotavirus gastroenteritis.

VEGETATIVE REACTIVITY OF CHILDREN WITH STREPTOCOCCAL TONSILITIS ON THE BACKGROUND OF HERPES VIRAL INFECTION

Streptococcal infection in children, its complications and adverse long-term consequences remain an urgent problem in pediatrics. Scientists continue to search for factors that shape the course of the disease. One of them is the timely and adequate response of the autonomic nervous system, which provides both short-term and long-term strategic adaptation of the organism. Violations of this adaptation can lead to the presence of comorbid conditions, which are increasingly common. The share of children is growing. infected with the herpes virus group, including human herpes virus type 6 (HHV-6).&#x0D; &#x0D; The aim of the work was to study the state of vegetative reactivity (VR) of children with streptococcal tonsillitis on the background of HHV-6 infection. In 68 children aged 4 - 15 years with tonsillitis of streptococcal etiology of moderate severity, vegetative reactivity was determined by cardiointervalography (CIG) followed by analysis of heart rate variability (CP) depending on the presence or absence of concomitant HHV-6 type of infection. The studies were performed in the acute period of the disease and in the period of early convalescence. The control group consisted of 20 healthy children, similar in age and sex. Static processing of the obtained results was performed using Excel and Statistica 6.0 using parametric and non-parametric research methods.&#x0D; &#x0D; Results.&#x0D; In the acute period of streptococcal tonsillitis in children of both groups there was a decrease in the humoral component in the regulation of the system and the level of activity of the parasympathetic ANS, as evidenced by a decrease in Mo and ΔX, independent of background, p&gt; 0.05. There was an activation of the influence of the sympathetic link of the VNS, increased the degree of centralization of heart rate control in all patients, and this was confirmed by an increase in AMO and IN. Prior to the convalescence period, CIG parameters were restored only in patients without concomitant VGL-6 infection, and the interrelationships of the sympathetic and parasympathetic links of the VNS were restructured with increasing role of the latter. In patients with concomitant VGL-6 infection, the values ​​of ΔX and IN differed significantly from the control group, p˂0.05. Thus, in children with streptococcal tonsillitis on the background of HHV-6 infection, there was a decrease in the level of functioning of the sympathetic VNS, but complete recovery did not occur, indicating instability of adaptation processes, depletion of the parasympathetic VNS, which hides the possibility of failure of adaptation, recurrence of the disease and / or chronicity, the development of secondary disorders of the cardiovascular system.&#x0D; Conclusions.&#x0D; The acute period of streptococcal tonsillitis is accompanied by stress of the sympathetic VNS, the severity of which does not depend on the presence of concomitant herpes virus infection. In the period of convalescence of streptococcal tonsillitis in the presence of children with HHV-6 infection there is no complete recovery of autonomic reactivity, among which the most informative are ΔX and IN.

Reassessment of Poststroke Dysphagia in Rehabilitation Facility Results in Reduction in Diet Restrictions

Background: Dysphagia assessment in postacute stroke patients can decrease the incidence of complications like malnutrition, dehydration, and aspiration pneumonia. It also helps to avoid unnecessary diet restrictions. The aim of this study is to verify if regular reassessment of dysphagia would change the diet management of postacute stroke patients in rehabilitation settings. Methods: This single-center retrospective study included 63 patients referred to an inpatient neurological rehabilitation center between 2018–2019. A standardized clinical swallowing evaluation and Fiberoptic Endoscopic Evaluation of Swallowing (FEES) were performed. Diet level according to Functional Oral Intake Scale (FOIS) was evaluated. As the primary endpoint, the FOIS values based on diagnostic procedures were assessed at hospital discharge, rehabilitation admission, and after FEES. Results: 19 women (30%) and 44 men (70%), with a mean age of 75 y (SD ± 10.08), were enrolled. The intergroup ANOVA revealed significant differences (p < 0.001) between dietary prescriptions in an acute care setting and following clinical and endoscopic reassessment in the rehabilitation center. Diet recommendations changed in 41 of 63 (65%) enrolled patients (p < 0.001). Conclusion: Instrumental diagnostic by FEES during the early convalescence period of stroke patients leads to clinically relevant changes to diet restrictions and lower rates of pneumonia. Our findings underline the need for regular and qualitative dysphagia diagnostics in stroke patients participating in neurological rehabilitation.

Clinical Value of Concentrations of Inflammation Immunochemical Markers in Blood Serum in Children with Viral Meningitis

A number of the immunochemical markers of inflammation in the blood serum, such as the lactoferrin, transferrin, ferritin, and fibrinogen were identified in 450 patients with the viral meningitis of various etiologies (enterovirus, arbovirus, mumps, adenovirus, and herpesvirus) at 14 years of age. The imbalance of the inflammation markers identified was determined, the severity of which depended on the severity, course and outcome of the disease. The decrease of the lactoferrin concentration by 29% (from 719 to 516 ng/ml) and increase of the ferritin level by 30% (from 70 to 91 ng/ml) by the period of the early convalescence met the heavy severity level of the meningitis. The decrease of the lactoferrin concentration by 2% (from 785 to 770 ng/ml) and increase of the ferritin level by 45% (from 68 to 99 ng/ l) by the period of early convalescence indicated the lingering course of the disease. The concentrations of the transferrin less than 2 g/l (1.74 to 1.68 g/l) and ferritin less than 50 ng/ml (40 to 48 ng/ml) were unfavorable prognosis of for the meningitis outcome.

Forms of pseudotuberculosis progression in children and the impact of lipid peroxidation activation and antioxidant system imbalance on their development

The objective is to compare clinical symptoms, lipid peroxidation indicators, the state of the antioxidant system and assess their impact on the severity and progression of pseudotuberculosis in children.Materials and methods. We examined 125 children with pseudotuberculosis divided into 4 groups according to the severity and nature of the disease progression and 45 healthy children. The material for the study was red blood cells and blood plasma of patients received in the dynamics – the acute period (during hospitalization); 3-4 weeks later – the phase of early convalescence with a non-smooth progression and moderate and heavy severity; the recovery period with a smooth progression and mild and moderate severity; 5-6 weeks later – the recovery period with a non-smooth progression and moderate and heavy severity. The spectrophotometric method was used to study lipid peroxidation (the concentration of diene conjugates, TBA-reactive substances) in the blood plasma and components of the antioxidant support system (the content of reduced glutathione; the activity of glutathione reductase, glutathione peroxidase, and catalase) in red blood cells.Results. It was determined that moderate and heavy pseudotuberculosis forms prevail in hospitalized children, the disease progression in 35.2% of them was non-smooth; lipid peroxidation products accumulate in the blood plasma and the concentration of reduced glutathione decreases in red blood cells during the acute period of pseudotuberculosis in all children relative to the parameters in the control group. In the period of early convalescence an imbalance in the functioning of antioxidant enzymes of red blood cells, as well as the accumulation of TBA-reactive substances and a decrease in the content of reduced glutathione were observed in patients with moderate and heavy pseudotuberculosis.Conclusion. The impact of the imbalance of pro-/antioxidants on the formation of predominantly moderate and heavy pseudotuberculosis in children is shown. Prognostic criteria for the development of a non-smooth progression of pseudotuberculosis are a high level of lipid peroxidation products in the blood plasma, no normalization in values of glutathione system components and the activity of erythrocyte catalase during early convalescence.

Клинико-патогенетическое значение нарушения антиперекисной защиты у детей с псевдотуберкулезом

Objective. To assess the impact of changes in the content of ceruloplasmin and the activity of myeloperoxidase, superoxide dismutase, glutathione peroxidase, catalase on an increase in the severity and development of a form of pseudotuberculosis progression in children, to determine prognostic criteria for the formation of a non-smooth progression of the disease. Patients and methods. 125 children with pseudotuberculosis of various severity and progression were examined. The control group consisted of 45 children with health group II. The content of ceruloplasmin, the total peroxidase activity of blood plasma, the activity of superoxide dismutase, glutathione peroxidase, catalase, and myeloperoxidase were determined. Results. An increase in the activity of superoxide dismutase, myeloperoxidase and catalase in the acute period of pseudotuberculosis in all groups of children was determined. During the period of early convalescence an increase in the activity of superoxide dismutase, myeloperoxidase, and catalase against the background of comparable values of ceruloplasmin and glutathione peroxidase activity was observed in children with severe pseudotuberculosis. Conclusion. The results of the study prove that the mechanisms of non-smooth progression formation and an increase in the severity of pseudotuberculosis in children are mediated by an imbalance in the functioning of antiperoxides. A decrease in the activity of glutathione peroxidase due to an increase in the functioning of catalase in erythrocytes, no increase in the content of ceruloplasmin in the blood plasma during the acute period and the period of early convalescence serve as a prognostic criterion for the formation of a more severe degree and non-smooth progression of pseudotuberculosis. Key words: children, pseudotuberculosis, oxidative stress, antioxidant system

Clinical and immunological features of activation of latent herpesvirus infection in children with rotavirus infection

The analysis of clinical parameters and indicators of immune response in rotavirus gastroenteritis in children aged 12 to 36 months infected with herpes viruses was performed. Verification of the diagnosis of RVI was carried out by isolating rotavirus antigen from the feces of patients by enzyme-linked immunosorbent assay (ELISA) and the corresponding IgM antibodies from the blood. Also, all children were examined for herpes virus infection types 1, 2, 4, 5, 6. The level of specific IgG and IgM to these herpesviruses was determined by ELISA. In the case of a positive result, the presence of DNA (qualitatively) was determined by polymerase chain reaction (PCR). PCR blood tests for the presence of herpesvirus DNA were performed twice, in the acute period of RVI and in the period of early convalescence. The first group included 71 children in whom rotavirus gastroenteritis occurred on the background of latent herpesvirus infection, in the second ¬ 15 children in whom during the early convalescence there was a reactivation of herpesvirus infection. The obtained data indicate that the activation of herpesvirus infection occurs against the background of reduced immunoregulatory index in the acute period of the disease, and in the period of early convalescence RVI is characterized by the preservation of elevated CD 16+ cells and proinflammatory cytokines (IL-1β and TNF-α). in our opinion, leads to a prolongation of clinical symptoms of rotavirus infection. Keywords: children, rotavirus infection, latent and active herpesvirus infection, cellular and humoral immunity, cytokines.

THE VALUE OF THE MICROBIAL FLORA OF THE NASAL AND OROPHARYNGEAL MUCOSA IN THE FORMATION OF CLINICAL AND IMMUNOLOGICAL FEATURES OF INFECTIOUS MONONUCLEOSIS IN CHILDREN

Objective. The article presents the results of studies to determine the significance of the microbial flora of the nasal mucosa and oropharynx in the formation of the clinical course and immune response in children with infectious mononucleosis (IM). Materials and methods. Under the supervision were 93 children aged three to nine years, patients with mononucleosis. In 32 children (first group), Streptococcus pyogenes at concentrations of 10-5 and higher was isolated during bacteriological examination of the mucosa of the nasopharynx and oropharynx. 30 (second group) - 10-4 degrees or less. In 31 (the third group), Staphylococcus aureus, Spirochetae buccalis, E. Coli and other bacteria, except streptococcus, were sown in smears from the mucous membrane of the nasoropharynx. The immune status of patients was assessed by indicators of levels of lymphocytes CD3+, CD4+, CD8+, CD22+ and the content of interleukins 1β, 4, TNFα. Results. The acute period of the mononucleosis in children of the first group was characterized more severe symptoms of intoxication, more severe morphological changes in the tissues of the tonsils, lymph nodes, liver and spleen. Also a significant decrease in the relative amount of CD3+, CD4+, CD8+ was observed compared with the indicators of children of the second and third groups. The increase in blood CD22+ content was more significant in children of the first group. The content of pro-inflammatory IL-1β and TNF-α in patients of all groups was significantly higher than in healthy children. The IL-4 increased in children of the second and third groups. In the period of early convalescence in children of the second and third groups, the relative content of CD3+, CD4+, CD8+ cells approached the corresponding indices of the control group. This was not observed in children of the first group. CD22+ levels in all observation groups decreased by the convalescence period, but remained high compared with the control group. In children of the studied groups, by the period of reconvalescence, a decrease in the levels of IL-1β, TNF-α is noted, more significant in children of the second and third groups. At the same time, in children of the first group, the level of pro-inflammatory interleukins by the period of reconvalescence remained at high numbers. The content of IL-4 was a significant difference in the indicators of its content in comparison with the digital characteristics of healthy ones in children of the second and third groups. Conclusion. An analysis of the results of the study found that the presence of streptococcus in its high concentration on the mucosa of the nosopharynx of children with mononucleosis already contributes to the formation of cellular immunosuppression and a pronounced reaction of pro-inflammatory interleukins at the initial stage of the disease, which, in general, leads to aggravation of the clinical manifestations of the disease and, in our opinion, may be a causative factor of a possible unfavorable course of the disease.&#x0D;

Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase

We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.

КЛИНИКО-ЛАБОРАТОРНАЯ ХАРАКТЕРИСТИКА НОВОРОЖДЕННЫХ ОТ МАТЕРЕЙ, ПЕРЕБОЛЕВШИХ ОСТРЫМ ВИРУСНЫМ ГЕПАТИТОМ В И ОСОБЕННОСТИ РЕАБИЛИТАЦИИ

Relevance. Viral hepatitis in women during pregnancy is characterized by etiological diversity and has the entire spectrum of manifestations characteristic of HB infections. In the structure of viral hepatitis in pregnant women, viral hepatitis B accounts for up to 70 %. In case of a woman's illness, infection of newborns during pregnancy is a leading factor for the development of HB and HC - a viral infection in children. At the same time, the nature of specific immunological markers in the blood of the mother and child is of particular importance for the development of neonatal NV or HC-viral infection. Objective: assessment of the rehabilitation of children from mothers with acute viral hepatitis B at various stages of pregnancy based on the study of the clinical and laboratory characteristics of this infection. Materials and methods.The study included 45 children whose mothers suffered from acute viral hepatitis during pregnancy. The diagnosis was verified in all children according to the data of clinical and laboratory studies with the determination of HBsAg, HBeAg, DNA, RNA of viral hepatitis. Results. The first group consisted of 16 (35.5%) children whose mothers had HBsAg in their blood. HB viral infection developed in the third trimester of pregnancy, childbirth took place in the acute period of the disease at the end of the third week of the icteric period. The second group – 19 (42.3 %) newborns, whose mothers also fell ill in the third trimester of pregnancy, but childbirth took place later on the third week of the icteric period 15 (33.3 %) or in the period of early convalescence 4 (8.8 %). At the same time, HBsAg in the blood of all mothers continued to be determined during the early and late period of convalescence. Unlike the newborns of the first group, only 2 (4.4 %) children in the second group had HBsantigenemia at the 2nd week of life. In 2/3 of the examined newborns, antibodies to HBsAg were detected in cord blood or in serum taken in the first days of life. At the same time, the mothers had no antibodies, despite the presence of HBsAg. It is necessary to pay special attention to the fact that in the presence of antibodies to HBsAg in the umbilical cord blood in these children of HBsAg, there was no antigenemia during the follow-up during the year. Antibodies to HBsAg were re-detected at the age of 5-6 months and only in 3 (6.6 %) children at the age of 12 months. Mothers of 10 (22.2 %) newborns of the 3rd group were ill with HBV infection in the 2nd trimester of pregnancy and childbirth took place during the period of convalescence, after 6-7 months after clinical recovery and release from HBsantigenemia. However, these infants had anti-HBs in the absence of HBsAg, which persisted for 3-6 months after birth. Conclusion: the above requires rehabilitation measures in newborns from mothers who have had acute viral hepatitis B during pregnancy in order to prevent the development of complications and chronicity of the process.

Asthenic Syndrome and Its Correction in Patients with Infectious Diseases

The data of the results of prescribing the drug Entop for asthenic syndrome correction in the period of early convalescence in patients with meningitis and leptospirosis have been presented in the article. Administration of Entrop showed significant improvement of patients’ attention deficit, auditory memory, improvement of activity and mood, reduced levels of physical and mental tiredness in patients with meningitis. Patients with leptospirosis showed a statistically significant improvement of active attention, long-term auditory memory, and activity after prescription of drug Entrop. 97.7% of patients showed good tolerance of Entrop. The obtained results enable to recommend the drug for correction of asthenic syndrome in patients with meningitis and leptospirosis.