During a prospective multicenter non-interventional observational study, a comparative assessment was made of the serotype structure of pneumococci circulating among healthy children under the age of 5 years and children of the same age group with signs of respiratory infections in the periods 2016-2018 and 2020-2022. Data on the serotype structure of pneumococci in the period from 2016-2018 were obtained from our previous works. In 2020-2022 the study included 2066 healthy children and 603 children with respiratory infections. Streptococcus pneumoniae and their DNA were detected in nasopharyngeal swabs by classical culture and molecular methods. Typing was carried out by molecular methods. On the territory of the Russian Federation, pneumococci belonging to the serotypes included in the 13-valent vaccine are being forced out of circulation and replaced by non-vaccine serotypes. Before the introduction of mass antipneumococcal vaccination (until 2015), the 13-valent conjugate vaccine covered from 66.2% to 92% of pneumococci, after the start of mass anti-pneumococcal vaccination in the period 2016-2018, coverage decreased to 57.3%. Between 2020 and 2022, coverage was less than 40%. The main “non-vaccine” serotypes/serogroups circulating in the Russian Federation are 15AF, 11AD, 23A, 9LN and 16F.

Recently, more attention has been paid to the role of indolamine-2,3-dioxygenase and aryl hydrocarbon receptor in maintaining a balance between immune reactivity and tolerance in various infectious diseases. It is known that the hallmark of COVID-19 is the activation of immuno-inflammatory pathways that induce indoleamine-2,3-dioxygenase, a key enzyme that catalyzes the metabolism of tryptophan along the kynurenine pathway, thereby changing the ratio of kynurenine/tryptophan in the blood serum of patients. An important property of SARS-CoV-2 is its ability to bind to aryl hydrocarbon receptor, which leads to an increase in intracellular expression of indolamine-2,3-dioxygenase and production of kynurenine at the initial stage of infection. Long-term activation of the aryl hydrocarbon receptor increases the production of interleukin-6, enhancing the inflammatory state and counteracting immune tolerance in the later stages of COVID-19. In aggregate, these data point to an important role of indolamine 2,3-dioxygenase and the aryl hydrocarbon receptor in controlling inflammation in patients with COVID-19. Dysregulation of the immune response not only threaten the host’s ability to cope with SARS-CoV-2, but can also predispose a person to secondary bacterial and fungal infections. Among the secondary infections that occur in patients with new coronavirus infection, COVID-19-associated invasive pulmonary aspergillosis is an important cause of death, although many aspects of the disease still remain unresolved. This review presents the current understanding of the importance of tryptophan metabolites and immunological factors in the pathogenesis of COVID-19 and invasive pulmonary aspergillosis.

Reactivation of Betapolyomavirus hominis (BKPyV) in kidney and hematopoietic stem cell recipients can lead to serious complications such as BKPyV-associated nephropathy followed by transplant rejection and BKPyV-associated hemorrhagic cystitis. Early diagnosis of the disease is hampering by the possible combination of infection of BKPyV with other post-transplant pathologies and the absence of specific symptoms. Replication of BKPyV is currently the only reliable prognostic sign of the development of long-term consequences, so patient management is basseting on monitoring the concentration of viral DNA. However, consistency between the results of determining the viral load and the development of post-transplant complications associated with BKPyV reactivation cannot be achieving without effective means of standardizing laboratory testing. This review covers the current understanding of the epidemiology; pathogenesis and the clinical features of the disease associated with BKPyV, and also considers in detail the current methods of laboratory diagnosis infection of BKPyV.

The review presents modern information of domestic and foreign authors about possible pathogenetic mechanisms of the virus effect on the fetus in the case of cytomegalovirus infection in pregnant women. Immunosuppressive changes, which are a feature of the physiological course of pregnancy, create favorable conditions for the development of active cytomegalovirus infection. The virus’s ability to infect a wide range of cells in vivo and trigger a set of molecular mechanisms causes changes in placental cell differentiation, which plays a key role in transplant transmission. The processes of formation of chronic placental insufficiency, which leads to hypoxia of the fetus and to delay of intrauterine development, are separately highlighted. The literary data on non-specific metabolic changes of the mother and placental activation of proinflammatory cytokines (TNF-α, IL-1β, IL2, IL-6 and IL-8), which occur in cytomegalovirus infection and are of significant importance in formation of hypoxia of the fetus have been analyzed.

In addition, the role of individual cells in preventing intrauterine infection is examined, namely the deciduous macrophages with antiviral activity, the deciduous natural killers and their activated toll-like receptors. The article also discusses the genetic predisposition to the development of manifest forms of EID, including the relationship of polymorphism of TLR2 and Arg753Gln genes with an increased risk of intrauterine infection of the fetus CMV.

Characteristic properties of the virus are pronounced genetic diversity, the ability to life-long persistence in various human organs and tissues (secretory glands, lymphatic cells, kidneys, etc.) and replication without cell damage, as well as suppressing cellular immunity. The article describes the issues of genotyping of virus and the relationship of some genotypes with certain organ pathology in newborns.

Background: Glecaprevir/pibrentasvir (GLE/PIB) is the first pangenotypic ribavirin-free regimen allowing for treatment duration as short as 8 weeks for the majority of patients with chronic hepatitis C (CHC) genotypes (GT) 1 to 6. The results of clinical trials showed good tolerability of GLE/PIB and high virologic response rate (mostly >95%) among different patient populations. The main objective of this study was to determine how the efficacy and safety of GLE/PIB translates into real-world clinical settings in Russia.

Materials and Methods: This was a prospective, multicenter observational study in patients with CHC who received the GLE/PIB regimen. The treatment regimen was prescribed by a physician in accordance with all applicable requirements before the enrollment in the study. Patients were observed for the duration of GLE/PIB therapy and at least for up to 12 weeks after the treatment completion. Real-world data were collected in patient records. Follow-up visits, procedures, and diagnostic methods followed physicians’ routine clinical practice.

Results: Overall 161 patients were enrolled in the study in 11 study sites of them 128 patients had sufficient follow-up data to assess sustained virological response 12 weeks [i.e. ≥70 days] after the end of treatment with GLE/PIB (SVR12). Overall, 127 out of 128 patients (99.2%) achieved SVR12. Depending on treatment duration the following SVR12 rates were achieved: 98.7% in 8-week group (75/76), 100% in 12-week group (49/49) and 100% in 16-week group (3/3). One patient failed to achieve SVR, the exact reasons of failure couldn’t be established by the Investigator.

Since only one patient didn’t achieve primary endpoint the following SVR12 rates were achieved in different subpopulations: 91.7% in patients with GT2 (11/12); 98.9% in non-cirrhotic patients (88/89); 99.1% in treatment-naïve patients (113/114); 99.1% in patients without HIV co-infection (116/117); 99.2% in patients younger than 65 years (120/121).

On the other hand, SVR12 was achieved by all patients (100%) in the following subpopulations: patients with GT3 (n=76), GT1a (n=5), GT1b (n=29) and other GTs (n=6); cirrhotic patients (n=36) and those with unknown cirrhosis status (n=3); treatment-experienced patients (n=14); HIV/HCV co-infected patients (n=11); patients older than 65 years (n=7); and drug users (n=10).

No clinically significant abnormalities in the key laboratory parameters were noted during the study. On contrary, the overall improvement of the liver enzymes was observed at SVR12 Visit. There were 3 patients with 3 adverse events (AEs): 2 cases were mild (cough and rash), and 1 case was severe and evaluated as a serious AE (hepatic decompensation). Hepatic decompensation led to the patient withdrawal from the study; this serious AE was preceded by 2 months of daily alcohol consumption and in the investigator’s opinion was not related to GLE/PIB intake. Of all AEs only rash was related to GLE/PIB administration according to investigator’s opinion.

Conclusion: GLE/PIB has proven to be a highly effective treatment regimen in the routine clinical practice in patients with all hepatitis C virus genotypes, including those with GT3 and compensated liver cirrhosis. SVR12 rates demonstrated in this study are fully consistent with the previously published data. The regimen was well tolerated by patients.

Introduction. Asthenic disorders due to COVID-19 infection are generally classified under a recently introduced category in ICD-10: U09.9 Condition after COVID-19, unspecified. In this regard, it is necessary to study the clinical manifestations and systematize the asthenic syndrome after coronavirus infection in order to better understand the tactics of treatment and rehabilitation of this group of patients.

Objective. To assess the prevalence of asthenic syndrome in patients who have had a coronavirus infection, to characterize and present its dynamics.

Materials and methods. The study involved 200 people with a confirmed diagnosis of COVID-19, aged 51 to 83, who were undergoing inpatient treatment. After discharge from the hospital after 6 months and 12 months, these patients again underwent a physical examination, anamnesis, complaints, and a questionnaire to identify symptoms of asthenia and other psychopathological syndromes.

Results. Asthenic symptoms were found in 2/3 of the examined persons. Autonomic disorders were noted with a slight decrease from 81.5% after 6 months to 74.2% after 12. Sleep disorders and increased fatigue progressed during the observed period from 70.4% to 80.6% and 63.0 to 74.2% respectively. Emotional lability of patients as a whole did not change.

Conclusion. Polymorphic symptoms of asthenic syndrome were revealed, the most common phenomena were sleep disorders and symptoms of fatigue.

Background: The disease that is endemic and has become a global pandemic is COVID-19 due to reports of thousands of cases. The pandemic is weighing on intensive care units with an influx of COVID-19 patients. The clinical manifestations of COVID-19 vary, diagnostic examinations and treatment are also experiencing dynamic developments. This study aims to provide an overview of the characteristics, clinical manifestations, length of treatment and nutritional status of COVID-19 patients who are hospitalized in the Isolation Room of Dr Soetomo Hospital Surabaya.

Methods: this study used a descriptive analytic cross-sectional method with inclusion criteria that were positive for COVID-19. The research data was obtained from 130 hospital medical records for the period June to August 2021. The collected data was then analyzed using SPSS version 25.

Results: The study found that men were more exposed to COVID-19 (71.5%) and 70% of patients worked as medical personnel. The age range of the majority of patients was more than 40 years (78.5%). Clinical manifestations of COVID-19 patients were cough (44.6%), fever (40%), flu-like symptoms (32.3%), painful swallowing (26.2%), anosmia (16.2%), shortness of breath (15.4%), nausea (14.6%), vomiting (13.8%), and diarrhea (0.9%). The average length of stay is 7-14 days (9.2%) with adequate nutritional status (14.6%).

Conclusion: The majority of COVID-19 sufferers are male, over 40 years old, with cough symptoms, and the most comorbid hypertension, as well as deaths from hypertension and the elderly. Better treatment is needed for people with COVID-19.

Objective: is to assess clinical and laboratory prognostic factors to develop a differential diagnostic model between the monoinfection of tick-borne encephalitis febrile form and the mixed infection of tick-borne encephalitis with Lyme borreliosis non-erythemal form at the onset of the disease.

Materials and methods. The clinical examination involving 56 patients with tick-borne encephalitis febrile form (mean age: 46.1±3.1 years) and 27 patients with the mixed infection of tick-borne encephalitis with Lyme borreliosis non-erythemal form (mean age: 47.2±3.2 years) has resulted in the assessment of 65 clinical and laboratory parameters in the first week of the disease including 14 indicators of standard and extended hemogram profiles and 6 blood leukocyte indices. Pearson’s goodness-of-fit test was used for statistical analysis. The predictive values of the parameters were determined by the odds ratio and ROC analysis with AUC. The logistic regression model was developed using STATISTICA 12.0.

Results. To make differential diagnosis between mono- and mixed infection at the onset of the disease the following hematological parameters with “average” or “good” predictive values can be used: band neutrophil count (AUC=0.65), the index of leukocytes and erythrocyte sedimentation rate ratio (AUC=0.66), erythrocyte sedimentation rate (AUC=0.70), neutrophil granularity intensity (AUC=0.66), neutrophil reactivity intensity (AUC=0.72) and reactive lymphocytes count (AUC= 0.72). A logistic regression model with a “very good” predictive value (AUC=0.83) is developed which includes the following four predictors: band neutrophil count, erythrocyte sedimentation rate, NEUT-RI and NEUT-GI in peripheral blood.

Conclusion. The model is allowed to make a differential diagnosis between the mono- and the mixed infection of tick-borne encephalitis with good sensitivity and specificity values in the first week of disease.

Purpose: to give a comparative characteristic of the clinical and laboratory manifestations of viral lower respiratory tract infections of various etiologies.

Object and methods: Medical information of 385 patients, who were hospitalized in the clinic of Pediatric Research and Clinical Center for Infectious Diseases in the period from 2016 to 2022, was retrospectively analyzed. Inclusion criteria: age from 1 month to 17 years; infectious diseases of the lower respiratory tract; extraction of respiratory viral nucleic acids in nasopharyngeal swabs by polymerase chain reaction. Upon admission, all children underwent: a physical examination, an examination by an otorhinolaryngologist, a complete blood test with a leucogram, determination of the level of C-reactive protein, and, if it necessary, a chest X-ray in two projections.

Results: Respiratory syncytial virus and rhinovirus dominated in the etiological structure of lower respiratory tract infection. Differences in the duration and severity of fever and manifestations of catarrhal syndrome in respiratory viral infections of various etiologies were established. Boca-virus and rhinovirus infections often caused severe damage of the lower respiratory tract with acute respiratory failure. Viral lower respiratory tract infections have such changes in the leucogram as an increase in neutrophils and band cells, which persist for 4-5 days of the disease. The severity of inflammatory changes in the haemogram depends on the etiology of the disease. The most significant changes, such as leukocytosis and an increase in the absolute count of neutrophils, were detected in adenovirus and rhinovirus infections.

Conclusion: There were age and clinical features of viral lower respiratory tract infections in children. Prolonged fever and identified inflammatory changes in the hemogram, often in combination with an increase in the level of C-reactive protein, in children with viral lesions of the lower respiratory tract explain the frequency of prescribing antibacterial drugs at any stage of medical care. To select the optimal therapy tactics, it is necessary to take into account the clinical and laboratory features of respiratory viral infections in patients with diseases of the lower respiratory tract.

Aim: to assess the dynamic changes of humoral immune responses against the S-protein of SARS-CoV-2 and vitamin D level in healthcare workers providing care to COVID-19 patients.

Methods. Repeated cross-sectional studies were conducted with an interval of 6 months (May-December 2021) including 170 healthcare workers of infectious settings. An enzyme linked immunosorbent assay was used for the quantitative detection of immunoglobulins G to SARS-CoV-2 and the vitamin D level in the blood serum.

Results. In 1.5 years after the start of the pandemic, 91.2% healthcare workers were seropositive to SARS-Co-V-2. In December 2021, this proportion became 98.8%, and the percentage of individuals with high antibodies level (>150 BAU / ml) raised from 49.4% to 77%. Increase in antibodies level induced by vaccination against SARS-CoV-2 was significantly higher in those who have had prior COVID-19 (1031 BAU/мл) compared to those previously vaccinated (367 BAU/ml). The vitamin D level was lower than reference values in 71.2% of health workers and did not correlate with the concentration of antibodies to SARS-Co-V-2.

Conclusion. SARS-Co-V-2 seroprevalence among healthcare workers reached almost 100% by the end of the second year of the pandemic. A greater increase in antibodies level after vaccination was observed in healthcare workers previously infected with SARS-Co-V-2 due to formation of hybrid immunity. We did not reveal the association between the vitamin D level and the humoral immune response to SARS-Co-V-2.

Objective – to study the dynamics of the level of neuron-specific enolase (NSE) and S-100 protein in blood serum and cerebrospinal fluid in children with various features of viral encephalitis course and outcome and to define their role in diagnostics and prognosis.

Material and methods. 48 children aged from 1 month to 15 years were examined. Analysis of the level of NSE and S-100 protein was performed by the method of hardphase immune-enzyme analysis.

Results. A reliable increase of the level of S-100 protein in blood serum was identified in comparison with the control group in both acute and reconvalescence periods. During acute period higher values of NSE in blood serum were found in children with herpesvirus encephalitis of various etiologies in comparison with varicella zoster encephalitis, and during reconvalescence period – higher values of S-100 protein. In case of the most severe course of the disease the level of NSE in cerebrospinal fluid was reliably higher in comparison with patients in severe condition. Children with convulsive syndrome demonstrated higher concentration of NSE in cerebrospinal fluid than patients without convulsions. In case of formation of stable neurologic deficiency during the disease outcome there was identified an increase of NSE concentration in blood serum in comparison with the recovered patients. It was also identified that if the values of NSE were >7.0 ng/ml, it was possible to predict unfavourable outcome of viral encephalitis with sensitivity of 61.54% and specificity of 71.43%. The highest values of neuron-specific proteins in blood serum were found in the dead patient with herpes encephalitis.

Conclusion. Analysis of NSE and S-100 protein in pediatric viral encephalitis is characterized by diagnostic and prognostic significance, demonstrates their role in pathogenesis and can be used for therapy correction.

Purpose. To study the features of the clinical course of coronavirus infection (COVID-19) in people living with HIV and risk factors for adverse outcomes.

Materials and methods. The study included 523 patients with a confirmed diagnosis of COVID-19 occurring against the background of HIV infection and hospitalized from March 2020 to September 2021 on the basis of the GBUZ “S.P. Botkin KIB” in St. Petersburg. Two groups were formed: 1 – receiving antiretroviral therapy (n=204), 2 – not receiving ART (n=319). A comparative analysis of the results obtained during the examination was carried out using statistical methods: Mann-Whitney (p≤0.05) and the calculation of the relative risk (RR) when comparing the probability of the outcome of the disease depending on the presence of risk factors: respiratory rate ( NPV),% lung damage, levels of CD4 and C-reactive protein (CRP) with a significance level of p≤0.05.

Results. Among the patients, persons aged 30 to 49 years predominated. In 50.5% of cases, coronavirus infection proceeded in the form of acute respiratory viral infections, pneumonia was diagnosed in 49.5%, which was subsequently complicated in 22.9% by the development of acute respiratory distress syndrome or sepsis in 2.1%. Severe course of COVID-19 was observed in non-adherent to ART, with CD4 lymphocyte count (≤50 cells/µl), multimorbidity and amounted to 45%.

Conclusion. A feature of the course of COVID-19 in patients with HIV/SARS-COV-2 coinfection was a high number of deaths – 21.6%. In the overall structure of causes of death, the maximum share fell on HIV infection – 58.4%, COVID-19 – 24.8%, HIV/ COVID-19 –9.7% coinfection and other causes – 7.1%. Factors associated with the development of severe forms of coronavirus infection caused by SARS-COV-2 in HIV-infected patients who were hospitalized, the combination of which can be used as a predictor of death, have been identified: respiratory rate (RR) > 20 per minute, percentage of involvement lungs> 50%, CD4 lymphocyte level <40 cells/µl, CRP>50 mg/l, presence of three or more concomitant diseases.

The purpose of the study: to determine the development of vaccination against infections associated with contingents in an epidemic crisis.

Materials and methods: the method of a sociological survey of future workers and those vaccinated in different epidemic status periods was used: 2019 – the pre-pandemic period and 2020 – the period of the COVID-19 pandemic. A sociological survey was conducted in 2019 among 212 medical workers (130 doctors and 82 nurses) and among 229 medical workers in 2020 (143 doctors and 86 nurses). Parents were also interviewed using a questionnaire. 100 and 50 respondents took part in the survey, respectively.

Results: a large number of pregnant workers – 74.3-88.1% are positive about vaccination. However, 6.8% of therapists and 9.6% of nurses of adult health facilities express a wary attitude, there were no negative reactions, unlike in 2019, when the severity of 2.2% of general practitioners and 4.2% of nurses of adult health facilities was negative. The largest number of respondents of all groups among the reasons for refusing to vaccinate is called “information that vaccinations are dangerous” from 76.6% to 88.9% in 20219, from 74.1% to 93.2% in 2020. Among parents, only 34% had a positive attitude towards vaccination, 12% negatively.

Conclusions: It is necessary to take prompt measures to increase adherence to vaccination of the main social groups that have a decisive influence on the attitude and effect of vaccination.

Aim – to evaluate the effect of direct antiviral drugs (sofosbuvir and velpatasvir) on the formation of the metabolic syndrome in patients with chronic hepatitis C with a high risk of its development 2 years after treatment.

Materials and methods. 112 patients with HCV (n=112) were examined, in whom the risk of developing the metabolic syndrome was determined using a specially developed method. In 58 patients, a high risk of developing metabolic syndrome was identified. This cohort of patients was divided into two groups: group 1 (n=26) who took sofosbuvir and velpatasvir and group 2 (n=32) who did not take AVT. Patients were periodically examined and observed for 2 years. At the final stage of observation, a comparative analysis of laboratory and instrumental data was carried out in patients in two comparison groups.

Results. At the start of AVT, HCV patients with a high risk of developing metabolic syndrome were found to be over-weight, moderately pronounced stage of liver fibrosis (F2 according to METAVIR), high viral load, increased transaminases, total low-density lipoprotein cholesterol, atherogenic coefficient, insulin, glucose. Two years after the etiotropic therapy in HCV patients with a high risk of developing the metabolic syndrome, normalization of blood lipid metabolism, glucose, insulin levels and a decrease in the concentration of total thyroxine were registered.

Conclusion. Etiotropic therapy with direct antiviral drugs in patients with chronic hepatitis C reduces the relative risk of developing the metabolic syndrome by 6,3 times.

Objective: To identify common and distinctive characteristics of the epidemical process of tick-borne encephalitis and Lyme borreliosis on the example of the Republic of Karelia.

Materials and methods. The frequency of infected tick bites, dynamics, intensity, territorial, gender, age and social features of the incidence of tick-borne encephalitis and Lyme borreliosis in 2000–2021 were analyzed according to official statistics, epidemiological examination of foci and laboratory studies. The results of studies of 2379 blood samples of adults who were not ill and not vaccinated against tick-borne encephalitis for the presence of antibodies to the virus were analyzed.

Results. The virulence of ticks in 2000–2021 decreased from 23.6 to 1.3%, infection with borrelia at the level of 13.4– 38.4%. The average long-term incidence rates of tick-borne encephalitis and Lyme borreliosis were 6.2 and 6.6 per 100 thousand, the dynamics of incidence had an average pronounced downward trend, correlated with the dynamics of requests for medical care of the population affected by ticks. The main clinical form of tick–borne encephalitis is meningeal (48%). Non-erythemic forms of borreliosis in recent years amounted to 39.1%. Antibodies of class G to tick-borne encephalitis virus were detected in 11.8±0.7% of the examined individuals. The territory of risk of infection with tick-borne encephalitis and Lyme borreliosis is the central and eastern part of the south of the Republic, where I.persulcatus dominates. The proportion of urban residents among patients with both infections is higher, but the incidence of urban and rural populations did not have significant differences. The incidence rates of tick-borne borreliosis in persons aged 40-49, 50-59 and 60 years and older are 1.6-2.2 times higher than those of tick-borne encephalitis, but the difference is not significant. At working age, the percent of men is higher than women, there are no differences among the elderly.

Conclusions: Similar and different features of the epidemic process of tick-borne encephalitis and tick-borne borreliosis have been identified, which should be taken to improving the detection of diseases, predicting the situation and planning preventive measures.

The article presents the results of the study and analysis of archival documents, on the basis of which the history of the construction of the complex of buildings of the garrison infirmary «York» in Königsberg is recreated, the features of the architectural and planning solutions used in the construction of this medical complex are studied and analyzed. The description of the post-war and modern stages of development of the infectious diseases hospital of the Kaliningrad region, which is located in the preserved buildings of the garrison infirmary «York» in Konigsberg, is given.

Crimean haemorrhagic fever (Crimean-Congo haemorrhagic fever) – an important public health problem due to the wide geographical spread, the ability to cause epidemic outbreaks of disease and high mortality. Evidence that human infection in some cases may occur in direct contact with the patient (bypassing the vector) indicates a high risk of contamination of surrounding people. This article presents a case of severe Crimean haemorrhagic fever in combination with tick-borne borreliosis with different clinical manifestations of the disease with many complications developed due to both direct and indirect effects of virus not only on blood cells, the system of hemostasis and vascular component with the development of hemorrhagic syndrome, but also on many organs and systems of the body. The possibility of long-term persistence of the Crimean haemorrhagic fever virus in the human body against the background of the inhibition of the immune system of the body and the severe course of the disease associated with the development of life-threatening complications, leads to a high risk of death, prolonged restorative treatment and extended hospitalization.

The first Russian clinical case of monkeypox in combination with herpes simplex type 1 infection in a 29-year-old man who returned from Portugal is described. The protocols for sequencing the virus genome are presented. Particular attention is paid to the difficulty of diagnosing vesicular rash in patients with a suspicious history.

We present a brief description of lethal case of meningococcal infection in 41 y old women, diagnosed by detection of Neisseria meningitidis in blood and results of histobacterioscopic study with the absence of rash and prominent mononuclear (non purulent) infiltration of soft meninges.