Since March 2020, the World Health Organization has declared a coronavirus infection pandemic. Almost immediately, the development of vaccines began, according to the recommendations published by WHO. Currently, 137 vaccines in the world are undergoing clinical trials and 194 are at the stage of preclinical studies. Candidate vaccines have been developed using a variety of technology platforms. This article presents data on the safety and efficacy of mRNA vaccines against a new coronavirus infection in children and adolescents. A high population effect of these vaccines was noted before the spread of Delta and Omicron variants and a slight decrease in effectiveness against new coronavirus variants. The results of the use of these drugs in patients at risk are also described: cancer patients and people with autoimmune and autoinflammatory diseases.

The review analyzed literature data on the safety and efficacy of mRNA vaccines against coronavirus infection. Currently used mRNA vaccines against novel coronavirus infection are safe and effective even among patients at risk (cancer patients and individuals with autoimmune or autoinflammatory diseases).

The results of studies and post-registration monitoring of mRNA vaccines emphasize their safety and efficacy profile, which confirms the possibility and need for mass use. 

Progress in the study of the human microbiome, in terms of its impact on the maintenance of health, is considered as one of the most significant achievements of modern biology and medicine. Studying the bacteria inhabiting the body, understanding the patterns of human interaction with the world of microorganisms, will help to better determine their role in general metabolism, influence on the functioning of various body systems, form a more accurate understanding of the pathogenesis of diseases, become the basis for the prevention of infectious diseases, and the implementation of microbial therapy of infections, obesity, diabetes.

The qualitative and quantitative composition of the microbiome, on which the future human health largely depends, affects the mode of birth and the nature and type of nutrition of the newborn.

Herpes zoster remains an actual problem for elderly patients and those with immunosuppression. Usually the clinic of Herpes zoster is considered as a combination of neuralgia and typical vesicular rash (sometimes with intoxication). However, the rash does not appear in all patients, and the spectrum of neurological manifestations of the virus reactivation is extremely wide. Most of them reduce the quality of life, and some may result in disability or even death. Due to polymorphic symptoms and difficulties in laboratory diagnosis, many cases of the disease may remain unrecognized, the patient will not receive the necessary etiotropic therapy, so the course of the disease will become more protracted, and the prognosis will worsen. This review is based on 62 domestic and foreign publications without limiting the depth of the search. Here we describe relatively rare forms of the disease with injury of the sensory and motor peripheral nerves, brain and cranial vessels. We offer You a detailed description of pain: herpetic and postherpetic neuralgia. Also in the article we describe examples of damage of motor neurons and give some basic information about damage to the central nervous system. A separate section is devoted to diagnostic methods. This section describes the advantages and disadvantages of diagnostic methods used in real clinical practice, indicates the materials for the study, and the markers of subclinical virus reactivation. The “treatment” section is mainly devoted to the peculiarities of etiotropic therapy for various forms of the disease (with an indication of the recommended drugs, their doses and duration of the course). At the end of the article a list of clinical indications for examination for reactivation of the herpes zoster virus is defined.

The results of our own long-term research on the effectiveness of specific prevention of viral infectious diseases using the example of tick-borne encephalitis are presented in the article. The peculiarities of the formation of the immune response during vaccination against tick-borne encephalitis are shown on the model of the vaccine preparation «Encepur® adult» (Germany). The terms of revaccination were substantiated, taking into account the ELISA parameters of the immunity intensity to the tick-borne encephalitis virus, equal to not less than 1: 400. The experiment shows the mechanisms of passive immunization of persons infected with the tick-borne encephalitis virus, based on the protective effect of specific antibodies. The established high level of immune protection during complex vaccination with drugs against tick-borne encephalitis from different manufacturers helps to understand its effectiveness in relation to vaccination against other infections.

Aim: to evaluate the efficacy and safety of convalescent plasma therapy for patients with severe SARS-CoV-2 infection.

Materials and methods: the study included 64 patients with laboratory-confirmed severe new coronavirus infection. The control group consisted of 58 patients who, in addition to standard therapy, received a transfusion of plasma from donors who had recovered from COVID-19. The effectiveness of immune plasma was assessed by the duration of fever, the level of oxygen (SpO₂ %) in dynamics, the detection of SARSCoV-2 RNA in nasopharyngeal and oropharyngeal swabs using PCR method in dynamics, as well as by the dynamics of blood tests results. Adverse events (any medically adverse events that occurred after immune plasma transfusion) were recorded as safety criteria.

Results: patients who received convalescent plasma, showed a significantly shorter period of SARS-CoV-2 replication compared with the control group. The use of immune plasma did not have a statistically significant effect on the duration of the fever, as well as the dynamics of blood oxygenation. Also, there were no significant differences compared with the control group when assessing blood tests parameters.

Conclusion: The use of COVID-19 convalescent plasma to treat severe COVID-19 did not show significant clinical effect but reduced the period of viral replication. It also showed no unexpected or serious adverse events. 

Purpose: to assess the relationship of platelet variables with the etiology, severity of community-acquired pneumonia in children and the main biomarkers of systemic inflammation.

Object and methods. The study included 65 children aged 9 months to 16 years 11 months with community-acquired pneumonia, who were treated at the clinic of Pediatric Research and Clinical Center for Infectious Diseases and the St. Olga City Children’s Hospital. Upon admission, the children underwent: complete blood count using a hematology analyzer (with the assessment of platelet parameters such as mean platelet volume, platelet distribution width, platelet large cell ratio), blood biochemistry (with the assessment of the C-reactive protein level), chest X-ray with radiographs in two projections. All children were examined for a wide range of pathogens of community-acquired pneumonia: respiratory viruses, S. pneumoniae, H. influenzae type b, M. pneumoniae, C. pneumoniae. The severity of pneumonia was assessed using the modified Respiratory Index of Severity in Children. Depending on the probable etiology, 4 groups of communityacquired pneumonia were identified: bacterial, viral, mycoplasma, and others.

The results of the study. No significant differences in platelet variables depending on the etiology of pneumonia were found. In mycoplasma pneumonia, platelet variables are inversely proportional to the total white blood cell count. During the infectious process, all patients showed a significant increase in platelet count. The platelet count on admission directly correlates with the absolute white blood cell count and absolute neutrophil count. There are no significant correlations of platelet count and C-reactive protein concentration.

Conclusion. There were no significant differences in platelet count depending on the etiology and severity of pediatric pneumonia. There are features of platelet variables in mycoplasma pediatric pneumonia.

Despite the rapid accumulation of facts about the humoral immune response in COVID-19, there are still no evidencebased answers to questions about the factors influencing the level and duration of the detection period of antibodies to SARS-CoV-2 in the blood.

Objective: To assess the prevalence, clinical and demographic associations of IgG antibodies to RBD of the SARSCoV-2 spike protein at different times after COVID-19.

Materials and methods. Residents of the Altai region of Russia, Caucasians aged 20-93 years, who had COVID-19 from May 2020 to February 2021 (n = 314), took part in a onetime observational study. The level of antibodies in the blood was measured by enzyme-linked immunosorbent assay 1-14 months after the onset of the clinical manifestation of COVID-19.

Results. Anti-RBD IgG antibodies of the SARS-CoV-2 spike protein were detected in 86.9% of the study participants. The dependence of the antibody titer on the duration of the period after COVID-19 was not revealed. The antibody titer was positively correlated with the complication of COVID-19 pneumonia and the volume of lung tissue lesions. The presence of pneumonia COVID-19 and the volume of lung tissue lesions are positively associated with age. Age positively correlated with antibody titer regardless of the pneumonia COVID-19 in the anamnesis.

Conclusion. IgG antibodies to RBD of the SARS-CoV-2 spike protein are present in most of the COVID-19 patients. The titer of these antibodies in adults depends on age, complications of pneumonia COVID-19, and probably persists up to 14 months after the first symptoms of infection appear.

The aim of the work was to evaluate the efficacy, safety and tolerability of etravirine-containing regimens in patients with treatment experience in real clinical practice.

Materials and methods. A retrospective analysis of 300 outpatient records of HIV-infected patients with treatment experience, which were converted to regimens containing etravirine (ETR) as the third component, was performed. The reasons for switching to ETR-containing regimens were adverse events, comorbidities, and virological failure. The main criterion for the effectiveness of the scheme was the proportion of patients with an undetectable level of viral load at 48 weeks of treatment. Additional criteria for evaluating the effectiveness and safety of the scheme were the dynamics of the number of CD4-lymphocytes, the frequency and nature of adverse reactions.

Results. The proportion of patients with virologic suppression less than 50 kop/mL was 83% versus 77,3% at the time of switching (p<0.005). The percentage of patients with CD4-lymphocytes level >500 ctlls/um increased from 40,3% to 58%, and the percentage of patients with CD4 level <200 cells/um decrease more than twice from 13% to 6% (p<0.005). The mean level os ALT decreased significantly from 47,52±66,45 units/L to 42,65±55,18 units/L (p=0,019). The average level of total cholesterol decreased by 8.7% from 5,64±1,37 mmol/L to 5.15±0.98 mmol/L (p<0,001). The average BMI after switching to ETR did not change and amounted to 24,07±4,07, 24,2±4,05, respectively (p=0,347).

Conclusions. The results of this study confirm that etravirine is well tolerated and may be an option for patients who have HIV RNA suppression on ART but develop adverse reactions, and may also be part of a second-line ART regimen in patients who fail first-line regimen.

Objective: to reveal the prevalence of infection by various variants of betaherpesvirus 6 А/В types in children with clinical manifestations of acute respiratory disease in case of betaherpesvirus 6 type DNA identification in the blood and to specify the features of diagnostic markers during mono- and mixed herpesvirus infection.

Materials and methods: there was made the analysis of clinical and laboratory data of 71 patients with the medical history of recurrent respiratory diseases or suspicion about exanthem subitum, hospitalized to Pediatric Research and Clinical Center for Infectious Diseases with the symptoms of acute respiratory disease and betaherpesvirus 6 type DNA identification in the blood. Laboratory investigation included molecular and biological methods of respiratory group and herpesviruses identification, as well as serological methods of antiviral antibodies identification.

Results: among the patients hospitalized with clinical manifestations of acute respiratory infection or exanthem subitum and presence of betaherpesvirus 6 DNA in the blood, 24, 0% of the patients had the markers of respiratory viruses in swabs taken from nasopharynx, 21,1% of the cases were diagnosed as viral-bacterial infection in the patients with a complicated course of the disease. 40,8% of the cases were registered as a mixed infection caused by betaherpesvirus 6 and Epstein-Barr virus. In 99% of the cases the patients were infected by human betaherpesvirus 6В; and in 1% of the cases - by human betaherpesvirus 6 А. One patient was characterized by a constant isolation of betaherpesvirus 6 А from his blood and oropharynx scrape in invariable concentration without any dependence on the administered treatment and the disease acuity.

Conclusions: betaherpesvirus 6 В was isolated in the blood of the patients in 99% of the cases, and 6 A – in 1% of the cases. The infection caused by Epstein-Barr virus was revealed more often in case of mixed infection by herpesviruses, with the markers of acute period or reactivation. The patient with confirmed betaherpesvirus 6 А had invariable virus load in his blood and oropharynx scrape that is likely to be connected with the virus genome integration in human cell DNA without provoking pathology.

Introduction. In the context of a pandemic of a new coronavirus infection (COVID-19), research on the peculiarities of the formation of an immune response to SARS-CoV-2 in patients who have been ill and vaccinated is of particular relevance. However, most studies are currently devoted to evaluating only the humoral link of immunity, and its cellular component remains insufficiently studied.

The aim of the study was to evaluate the features of the formation and changes of the T-cell link of immunity in patients with a new coronavirus infection and vaccinated against this disease.

Materials and methods. The study was performed on the basis of the clinical and diagnostic laboratory of the European Medical Center “UMMC-Health “LLC. Specific T-cell immunity was evaluated using ELISPOT technology. In the course of the study, 72 blood samples of employees of medical organizations were analyzed, including 26 from those who had a new coronavirus infection, 23 from persons who were intact according to COVID-19 before vaccination and 23 from the same employees after vaccination («Gam-CovidVac»).

In addition, each of the study participants was examined to determine specific class G antibodies (IgG) by solid-phase enzyme immunoassay using SARS-CoV-2-IgG-ELISA-BEST test systems (manufactured by VECTOR-BEST JSC).

Results and discussion. In the group of patients (26 people), T-lymphocytes capable of specifically reacting to SARSCoV-2 antigens were detected in 100% of cases, even in individuals with IgG elimination. It should be noted that the response was more pronounced when meeting with M-and N-pepdids, compared with S-protein.

22 out of 23 COVID-19 intact individuals had no T-cell immunity to coronavirus infection before vaccination, but one employee had a response to 3 proteins-M, N, S, which indicates that he had previously encountered the SARS-CoV-2 virus. After vaccination with the drug “Gam-Covid-Vac”, 22 (95.6%) employees revealed a T-cell response, while 21-only to S-protein, and an employee with a previously detected immune response-after vaccination, the response to M -, Nproteins remained almost at the same level, and the cellular response to S-peptide doubled.

Conclusion. Thus, based on the results of the study, important materials were obtained on the peculiarities of the formation of a specific T-cell immune response to a new coronavirus infection. The obtained data provide a broader understanding of the immune response in new coronavirus infection in patients who have been ill and vaccinated and can be used in the future when planning preventive and antiepidemic measures.

The incidence of the new coronavirus infection (COVID-19) remains a global problem worldwide. However, the effect of COVID-19 on the course of pregnancy and the possibility of intrauterine infection are insufficiently investigated. Recent studies suggest the possibility of a transplacental transmission of infection caused by SARS-CoV-2.

Goal: To analyze SARS-Cov-2 RNA detection cases in newborns and to study possible factors influencing the infection of newborns from mothers with COVID-19.

Materials and methods. From March to August 2020, there were 64 births to women with a confirmed diagnosis of COVID-19 at the Botkin’s Infection Disease Hospital. In 15 newborns, the diagnosis of COVID-19 was laboratory confirmed. In this study, the histories of 14 newborns and their mothers were analyzed retrospectively. The diagnosis of COVID-19 was based on the detection of SARS-Cov-2 RNA in a nasopharyngeal swab or in fecal samples.

Results. Analysis of the histories of mothers showed that 4 (28.6%) patients had an asymptomatic disease. Three (21.4%) women had a severe course of COVID-19, 7 (50%) patients had a course of moderate severity. Fetal hypoxia was more common in women with severe or moderate course of COVID-19. In 6 (42.7%) newborns, a positive nasopharyngeal swab was obtained within 48 hours after birth. None of the women whose children were RNA-positive in the first two days had a severe form of the disease, and two patients had an asymptomatic disease.

Conclusion.
1. The frequency of detection of SARS-CoV-2 RNA in newborns from mothers with COVID-19 (under mother-child separation) was 21.9%.
2. Infection of a newborn with SARS-CoV-2 is possible both with a severe course of the disease in the mother and with an asymptomatic course.
3. A caesarean section does not exclude the possibility of a newborn infection with SARS-CoV-2.
4. In newborns, in most cases, an asymptomatic course of COVID-19 is observed.

The aim of the work was to identify risk factors for the absence of a microbiological effect when using complex probiotic therapy in patients with drug-resistant tuberculosis.

Material and methods. The object of the study was 30 patients with tuberculosis in the course of anti-tuberculosis therapy, who received a course of complex probiotic therapy. The patients were divided into groups according to the microbiological effect of using the probiotic against Bifido and Lactobacterium spp .: Group 1 – restoration of Lactobacterium spp. Happened, 2 – did not happen, 1A – recovery of Bifidobacterium spp. Happened, 1B did not happen. With the help of statistical processing of the material, the main risk factors for reducing its effectiveness have been identified.

Research results. Among all factors (gender, social status, HIV infection, immunodeficiency, smoking, alcohol dependence, clinical form of tuberculosis and anti-tuberculosis drugs taken), the risk of reducing the efficiency of the Lactobacterium spp. in tuberculosis patients it is shown in males (OR 2.500, p = 0.029) over the age of 50 (p = 0.008). However, a significant decrease in the effectiveness of complex probiotic therapy to restore the pool of Lactobacterium spp. in the intestinal biotope is statistically significant due to the male sex (OR 8,000, p = 0.013 and the number of CD4 + lymphocytes (p = 0.005).

Conclusion. The main risk factors for a decrease in the rate of recovery of the pool of Lactobacterium spp. in patients with multidrug-resistant tuberculosis, the pathogen was male and female, and the recovery of the Bifidobacterium spp. depended on the male sex and the severity of immunodeficiency in the presence of HIV infection.

The purpose is improving the prediction of the immune status dynamics in children with HIV infection, taking into account independent predictors.

Materials and methods. Clinical, immunological, molecular genetic examination of 91 pairs «HIV-infected mother – child with HIV infection» was carried out. All children did not receive antiretroviral therapy. The age of children at the time of immunosuppression development was determined. The criterion for immunosuppression at the age of less than 1 year was a decrease in the number of CD4 lymphocytes to 30–35% (1,0–1,5 × 10⁹  / l), at the age of 1–5 years – to 25–30% (0,75–0,999 × 10⁹  / l), over the age of 5 years – up to 20–25% (0,35–0,499 × 10⁹  / l). To determine the factors affecting the rate of development of immunosuppression, we used mathematical models for analyzing the time to event (survival) and proportional Cox intensities.

Results. All children aged 9–54 months (median 22 months, interquartile interval 13-42 months) developed immunosuppression. Using a mathematical model of proportional Cox intensities, we tested anamnestic, clinical and laboratory parameters characterizing the state of health, HIV status of the mother, the course of pregnancy and childbirth, chemoprophylaxis of vertical HIV transmission, pathology of the neonatal period in children. Statistical significance in the multivariate model was demonstrated by the indicators «Lack of HIV vertical transmission chemoprophylaxis» (odds ratio 2,5; 95% confidence interval 1,4–7,7; P = 0,033) and «Congenital herpesvirus infection» (odds ratio 3,0; 95% confidence interval 1,3–6,9; P < 0,001).

Conclusion. All children with HIV infection quickly developed immunosuppression. The independent factors influencing the timing of the immunosuppression development were the lack of HIV vertical transmission chemoprophylaxis and the congenital herpesvirus infection. The results of the study make it possible to recommend expanding the coverage of HIV-infected pregnant women and their children with three-stage vertical HIV transmission chemoprophylaxis and improving measures for the diagnosis and treatment of congenital herpesvirus infections.

Introduction. Polymorphism of cytokine genes is a factor of susceptibility or resistance to infection, the development of the disease and a long, complicated course of influenza.

Objectives. Study of the lymphocyte-platelet adhesion function in patients with influenza A (H3N2) depending on polymorphic variants of the IL-2 gene promoter (T330G).

Materials and methods. The study included patients with influenza. Determination of SNP genes was carried out by PCR using standard kits of the Scientific and Production Company “Litekh” (Moscow). The examine of LPA was carried out by the method of Yuri Vitkovsky et al. (1999).

Results. During the immunogenetic study the effect of the polymorphism of the IL-2 gene promoter (T330G) on the function of lymphocyte-platelet adhesion in patients with influenza A(H3N2) was studied. It was found that in the group of patients with influenza the occurrence of polymorphic variants of IL-2 (T330G) significantly differed from the control group.

The major T allele significantly prevailed in patients compared with the group of healthy individuals with the predominance of the homozygous T/T genotype of the IL-2 gene promoter (T330G) (2.2 times) compared with the control group.

Conclusions. Indicators of the function of lymphocyteplatelet adhesion in influenza A(H3N2) depend on the carriage of genotypes of the IL-2 gene promoter polymorphism (T330G).

Objective: Comparative analysis of antimicrobial resistance of S. Enteritidis, S. Infantis, and S. Typhimurium isolated from humans, farm animals, and animal products.

Materials and methods. 898 Salmonella strains isolated from humans (673), farm animals (132), and animal products (93) were studied. Antimicrobial susceptibility was determined according to the EUCAST recommendations. The detection of beta-lactamase genes was performed by PCR. The mutations in the QRDR region of the gyrA gene were determined by amplification and direct sequencing of the internal fragment of the gene.

Results. Antimicrobial resistance in 69,9% of strains isolated from humans, 78,5% – from food, and 88,6% – from farm animals was detected. 68,7% of S. Enteritidis strains isolated from humans, 61,4% from food, and 21,1% isolated from animals were resistant to quinolones. The proportion of MDR S. Typhimurium strains ranged from 21,6% to 88,2%, depending on the source of isolation. From the S. Infantis strains 89,3% of strains isolated from humans, 94,5% – from animals and 97,8% – from food were resistant to antimicrobials, 67,9% of strains isolated from humans, 80,0% – from food and 89,0% ‒ from animals were MDR. The production of beta-lactamases TEM-1, CTX-M1, CTX-M2, and CMY-2 was detected. Resistance to quinolones was determined by a chromosomal mechanism: single-nucleotide substitutions in the gyrA gene were identified: Asp87Tyr, Ser83Phe, Asp87Asn, Ser83Tyr.

Conclusion. Antimicrobial susceptibility in Salmonella of dominant serovars had specific traits. Strains isolated from animals differed significantly from strains from humans and animal products. Resistance to quinolones and beta-lactams in Salmonella, regardless of the source of isolation and serovar, was due to molecular mechanisms universal for Enterobacteriacae.

The article reflects the history and evolution of the scientific activities of the research institute, now the Pediatric Research and Clinical Center for Infectious Diseases. The mission, strategy and current scientific directions are presented. The main achievements over the past five years are reflected, the introduction of which into the practical work of medical institutions in our country testifies to the effective implementation of the Mission of the institution to save the lives of children.

The problem of the non-smooth course of COVID-19 and deaths in children with severe comorbid pathology is urgent. Among all registered cases of a new coronavirus infection in the Russian Federation, children account for up to 8,6%, of which severe forms are noted, as a rule, in patients with concomitant diseases. A clinical observation of the course of a new coronavirus infection in a child with a severe form of idiopathic aplastic anemia complicated by pancytopenia is presented. COVID-19 infection caused a sharp deterioration in the child’s condition. Despite the use of modern methods of therapy, there was a rapid deterioration of clinical and laboratory parameters: an increase in febrility, respiratory failure, interstitial changes in the lungs, a decrease in oxygen saturation to 70%, hemorrhagic, anemic syndromes and multiple organ failure with the development of a fatal outcome. Aplastic anemia is a factor predisposing to the severe course of COVID-19 and contributing to an unfavorable outcome.