BackgroundEbola virus disease (EVD) is one of the most dangerous and lethal diseases affecting humans. There are several licensed vaccines against EVD, but it remains one of the priority diseases for research and development of effective vaccines.MethodsA double-blind randomized placebo-controlled trial was performed to evaluate safety and immunogenicity of rVSV- and rAd5-vectored vaccine GamEvac-Combi in healthy adults of both sexes between 18 and 60 years. Safety and immunogenicity were assessed during the observation period of 12 months. Immunogenicity was assessed with GP-specific ELISA, IFN-γ ELISA, and plaque pseudoneutralization assay.ResultsVaccinated participants showed marked GP-specific IFN-γ response at day 28 and neutralizing response at day 42 (GMT = 32.6, seroconversion rate 96.3%). GP-specific IgG antibody levels in vaccinated participants peaked at day 42 (GMT = 9345) and persisted for a year after vaccination (GMT = 650).ConclusionThe vaccine showed favorable safety profile and induced robust cell-mediated immune response and strong humoral immune response that lasts at least for a year from the start of vaccination.Clinical trial registrationClinicalTrials.gov, identifier NCT03072030; Pan African Clinical Trial Registry, identifier PACTR201702002053400.

Introduction. SARS-CoV-2 infection causes immune disorders that create conditions for the reactivation of human herpesviruses (HHVs). However, the estimates of the HHVs effect on the course and outcome of COVID-19 are ambiguous. Аim – to study the possible relationship between the HHV reactivation and the adverse outcome of COVID-19. Materials and methods. Postmortem samples from the brain, liver, spleen, lymph nodes and lungs were obtained from 59 patients treated at the Moscow Infectious Diseases Hospital No.1 in 2021–2023. The group 1 comprised 39 patients with fatal COVID-19; group 2 (comparison group) included 20 patients not infected with SARS-CoV-2 who died from various somatic diseases. HHV DNA and SARS-CoV-2 RNA were determined by PCR. Results. HHV DNA was found in autopsy samples from all patients. In group 1, EBV was most often detected in lymph nodes (94%), HHV-6 in liver (68%), CMV in lymph nodes (18%), HSV in brain (16%), VZV in lung and spleen (3% each). The detection rates of HHVs in both groups was similar. Important differences were found in viral load. In patients with COVID-19, the number of samples containing more than 1,000 copies of HHV DNA per 100,000 cells was 52.4%, in the comparison group – 16.6% (p 0.002). An association has been established between the reactivation of HSV and HHV-6 and the severity of lung damage. Reactivation of EBV correlated with increased levels of liver enzymes. Conclusion. Reactivation of HHVs in patients with fatal COVID-19 was associated with severe lung and liver damages, which indicates a link between HHV reactivation and COVID-19 deaths.

Introduction. COVID-19 is characterized by a varied clinical course. The aim of the work was to identify associations of SNPs of hemostatic system genes with COVID-19. Materials and methods. DNA was isolated from patients (n=117) and healthy participants (n=104). All infected patients were divided into 3 groups, depending on disease severity assessment, which was appreciated by NEWS2. Another group consisted of participants, who had asymptomatic infection in the past. Determination of SNPs of the genes FGB (-455 G/A), FII (20210 G/A), FV (1691 G/A), FVII (10976 G/A), FXIIIA1 (103 G/T), ITGA2 (807 C/T), ITGB3 (1565 T/C), SERPINE1 (-675 5G/4G) were performed by PCR using the Genetics of Hemostasis kit (DNA-Technology, Russia). Results. In analyzed SNPs, no significant differences were detected between the group of infected patients and healthy participants. But significant association was revealed in gene SERPINE1 (-675 5G/4G), when patient groups, differing in the disease severity, were analyzed relative to the group of participants with asymptomatic infection (p=0.0381; p=0 .0066; p=0.0009). It was found, that as COVID-19 severity scores increased, the proportion of 5G allele of gene SERPINE1 decreased, and the proportion of the 4G allele increased (p=0.005; p=0.009; p=0.0005). Similar processes were observed for genotypes 5G/5G and 4G/4G. Discussion. The gene SERPINE1 (-675 5G/4G) is associated with the severity of COVID-19. Conclusion. For the first time, it was discovered that 5G/5G genotype of gene SERPINE1 (-675 5G/4G) can be a marker of a milder course of COVID-19, and the 4G/4G genotype as a more severe one.

BACKGROUND: This study was conducted to determine the characteristics of various viral respiratory pathogens spreading during the epidemic season 20212022 and the frequency of co-infection with SARS-CoV-2 and influenza. AIM: To assess the development of the influenza epidemic and frequency of cases of co-infection with respiratory pathogens in patients with acute respiratory viral infections between 2021 and 2022. MATERIALS AND METHODS: Traditional and hospital epidemiological surveillance methods for acute respiratory viral infections were used. RESULTS: The epidemic season of 20212022 was characterized by the early activity of the influenza A(H3N2) virus and the emergence and rapid spread of the omicron variant of SARS-CoV-2. The distribution of different respiratory pathogens during the epidemic season 20212022 was clearly traced: SARS-CoV-2 (18.8%) was predominant, followed by influenza viruses (10.6%) and pathogens of other acute respiratory viral infections (0.43.7%). With respect to influenza A (H3N2) and B viruses, the heterogeneity of their populations and drift variability in relation to vaccine strains were noted. DISCUSSION: The frequency of co-infection with various respiratory pathogens was low, i.e., it was no more than 0.1%according to traditional surveillance, and no more than 9.2% in the hospital surveillance. The rationale for updating the composition of influenza vaccines for the countries in the Northern Hemisphere for 20222023 season was identified. CONCLUSION: At present, early diagnosis of influenza is important given the availability of effective drugs with a direct mechanism of action for the prevention and treatment of this pathogen. Timely use of anti-influenza drugs will reduce the risks of a severe course, complications, and death, including co-infection with SARS-CoV-2.

Relevance. The long-term leadership of ARVI pathogens determines their significance in the damage caused to both health and the economy of the country. Aim. To identify the features of the structure of ARVI during the emergence and widespread spread of SARS-CoV-2. Materials and methods. The article uses methods used in epidemiological surveillance of acute respiratory viral infections. Results and discussion. The results of the diagnostic available ARVI pathogens monitoring during epidemic seasons 2018-2021 are presented. The tendency of greater engagement of aged group 15 y.o. and older in epidemic process by morbidity and hospitalization due to SARI was shown. 49 818 nasal swabs from patients with influenza infection, 36 044 – with ARVI and 59 062 – with SARS-CoV-2 were tested. The top three in the structure of ARVI were INF, HEV-D and HRSV (in the 2018–2019 season); INF, SARS-CoV-2 and HEV-D (2019–2020); SARS-CoV-2, HEV-D and HPIV/HCoV (2020–2021). The activity of viral pathogens also differed: for HPIV, HAdV, HEV-D, HMPV, a decrease in activity was noted during the appearance of SARS-CoV-2 (2019–2020) and some of its growth in the following season; in relation to HRSV and INF - a decrease in activity during the last two seasons, and for INF – extremely low activity in the 2020-2021 season; the activity of seasonal HCoV even increased slightly. The data of genetic analyses of SARS-CoV-2 positive samples showed the heterogeneity of its population with a representative of variants (Alfa, Delta) as well as endemic for Russia and Moscow variants only. The recommended composition of influenza virus vaccines for use in the 2021–2022 northern hemisphere influenza season and in the 2022 southern hemisphere influenza season are presented due to their drift changeability. Conclusions. SARS-CoV-2 was influenced by the activity of ARVI pathogens with the almost complete displacement of influenza viruses from the circulation in the period 2020–2021.

Chickenpox is a common disease leading to a large number of clinical manifestations, ranging from mild spontaneously resolving forms to severe complicated cases requiring hospitalization and parenteral therapy. Despite the fact that this infection is benign in the majority of cases, it can lead to disseminated life-threatening processes in pregnant women and unimmunized newborns infected during the perinatal period, as well as it can cause intrauterine death and fetal abnormalities.Currently, there are no unified therapeutic approaches in the management of pregnant women with chickenpox. The nature and severity of infection in children depends on the moment of infection (before or after birth, intrapartum), the immune status of the mother against the human herpesvirus type 3 (HHV-3), the gestational age of the fetus and the presence of concomitant conditions.

This review presents the data on the spreading of all known human herpesviruses (НHVs) in female urogenital tract. According to the WHO almost 500 million people worldwide suffer from genital infection caused by НHVs. НHVs were detected in various inflammatory diseases of female upper and lower genital tract (vaginitis and cervicitis), in extrauterine pregnancy (in fallopian tubes), in infertility (cervical channel, endometrium and ovaries). Herpes simplex virus 1 (HSV‑1) was identified for the first time in oocytes after failed in vitro fertilization (IVF). НHVs produce negative effect on the entire reproductive process from conception to childbirth. It was established that HSV, cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) markedly increase the risk of spontaneous abortion, preterm birth and stillbirth. Intrauterine НHV infection is a major cause of congenital malformations. Data on humoral and cell immunity in genital herpesvirus infections (НHVI) are also reviewed. Intravaginal HSV‑2 infection changes cell composition of vaginal mucosa, i.e., together with cells mobilized from the blood, protective role is performed by resident memory T‑cells (TRM), natural killer cells (NK‑cells) and regulatory T‑cells (Treg) whose function consists in maintaining the balance of the activities of lymphocytes. Constant НHVI spreading is largely explained by transition of primary infection to potentially reactivating latent form, since latent virus is unavailable to immune recognition and medicines. The genome editing system CRISPR/Cas9 can recognize and modify not only active but also latent viruses. The promising pilot results with the use of this system offer the possibility of developing innovative technologies for НHV elimination and НHVI eradication.

The Epstein-Barr virus (EBV), one of the most common in the human population, is capable of lifelong persistence in resting memory B-cells, in T-cells in case of type 2 EBV, and in some undifferentiated epithelial cells. In most people, EBV persistence is not accompanied by significant symptoms, but frequent virus activations are associated with the increased risks of severe diseases, such as chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis, multiple sclerosis, systemic lupus erythematosus, gastric and nasopharyngeal carcinomas, and a variety of T- and B-cell lymphomas. Therefore, the molecular viral and host cell processes during asymptomatic or low-symptom EBV persistence are of great interest. This review describes the behavior of the viral DNA in an infected cell and the forms of its existence (linear, circular episome, chromosomally integrated forms), as well as methods of EBV genome copying. Two closely related cycles of viral reproduction are considered. Lytic activation is unfavorable for the survival of a particular viral genome in the cell, and may be a result of differentiation of a latently infected cell, or the arrival of stress signals due to adverse extracellular conditions. The EBV has a large number of adaptive mechanisms for limiting lytic reactivation and reducing hostility of host immune cells. Understanding the molecular aspects of EBV persistence will help in the future develop more effective targeted drugs for the treatment of both viral infection and associated diseases.

Here, we present the results of a study in which 639 samples obtained between October 2018 and April 2019 from patients with symptoms of acute gastroenteritis were tested for the presence of a rotavirus infection. The antigen of group A rotavirus was detected in 160 samples (25% of those tested). To study the genetic diversity of group A rotavirus, RNA was isolated from the samples, and polymerase chain reaction combined with reverse transcription (RT-PCR) with primers specific for the VP4, VP6, and VP7 genes of group A rotaviruses was performed. At least one fragment of the group A rotavirus genome was found in 101 samples (15.8%). These fragments were sequenced, and their G and P genotypes-as well as their combinations-were determined. The predominant G genotypes were G9 (35.8% of all genotyped samples) and G4 (28.4%), but the rare G12 genotype was also found (3.0%). The dominant P genotype was P[8]. The spectrum of certain G/P combinations of genotypes included seven variants. The most common variants were G9P[8] (37.2%) and G4P[8] (30.2%).

Cytomegalovirus infection (CMVI) with clinical manifestations is a valuable problem in patients with immunosuppression, particularly in patients with inflammatory bowel disease (IBD) treated with steroids and other immunosuppressive drugs. Clinical activity of cytomegalovirus-associated IBD, natural history and stage of IBD, steroids use and anti TNF-a-agents were identified as risk factors. CMVI diagnostics should clarify not only the presence of CMV but its etiological role in clinical features of the disease. The most significant are the virologic and serological methods. All patients with steroid resistance, loss of effect and severe IBD should undergo CMVI screening. It is likely that joining CMVI to IBD is one of the main causes of resistance to steroids, immunosuppressive and biological treatment. requires further studies.

Epstein – Barr virus, related to herpes viruses, causes infectious mononucleosis during the initial infection; after recovery, the virus persists in the body throughout lifetime. The presence of clinical symptoms and viral load in a patient in 6 months after the infectious mononucleosis disease indicates the formation of chronic active Epstein – Barr viral infection. Hemophagocytic lymphohistiocytosis, posttransplantation lymphoproliferative disease and chronic fatigue syndrome, which has a polyetiological nature, are also associated with the activation of the persistent Epstein – Barr virus. Most of these diseases develop in children due to their physiological immunodeficiency and are accompanied by high mortality – up to 50%. Immune mechanisms, in addition to the virus itself, play a leading role in the pathogenesis of the diseases. The article summarizes all existing approaches to the treatment of chronic Epstein – Barr virus-associated diseases. The authors have analyzed the effectiveness of these approaches on the basis of various published studies. These diseases are treated with etiotropic antiviral drugs – nucleoside analogs, nonspecific immunotherapy, targeted therapy with monoclonal antibody preparations, immune cellular CD8+ therapy. In case of ineffectiveness of these methods, the alternative bone marrow transplantation is used. The article highlightes promising areas for the development of new approaches to the treatment of Epstein – Barr virus-associated diseases.

Objective. To identify the drift variability of influenza viruses during the period of epidemic rise in the incidence of acute respiratory viral infections in the period 2018-2019. The biological and molecular-genetic properties of epidemic strains isolated in certain territories of the Russian Federation were studied and compared with data from the countries of the Northern Hemisphere. Materials and methods. A range of laboratory diagnostic methods has been applied, including immune fluorescence, RT-PCR, sequencing, methods for determining sensitivity to influenza drugs and receptor specificity. Results and discussion. The proportion of influenza viruses was as follows: A (H1N1) pdm09 - 53 %, A (H3N2) - 46 %, B - about 1 %. Cases of severe acute respiratory infections have most often been associated with influenza A(H1N1) pdm09 virus. According to antigenic properties, isolated strains corresponded to the properties of vaccine viruses (A/Michigan/45/2015 - by 99.6 % and A/Singapore INFIMH-16-0019/2016 - by 86 %). The heterogeneity of influenza A virus strains population was revealed as regards individual mutations in hemaglutinin. The influenza B virus population was equally represented by both evolutionary lines (B/Victoria and B/Yamagata-like). Receptor specificity was favorable for the course and outcome of the disease. Among 70 studied epidemic strains, no strains resistant to anti-neuraminidase drugs, oseltamivir and zanamivir, were detected. The article presents WHO recommendations on the composition of influenza vaccines for the countries of the Northern Hemisphere for 2019-2020, provides data on cases of human infection with avian influenza viruses A(H5N1), A(H5N6), A(H7N9) and A(H9N2).

Relevance. Influenza viruses, having an extremely high variability of the genome and significant environmental plasticity, continue to maintain a potential threat to the biological safety of mankind. The purpose Aims of the work is to analyze the features of the epidemic season of2017-2018. Materials and methods . The collection of data on the incidence and laboratory diagnosis of influenza and ARVI was carried out in the framework of the epidemiological surveillance of the circulation of influenza viruses in the Russian Federation. The observation period was from 40 weeks (october) 2017 to 25 weeks (june) 2018. The typing of the isolates was performed in the reaction of inhibition of hemagglutination activity (HI) according to the standard technique with diagnostic sera to reference and epidemic influenza viruses. Results and discussion . The article presents the features of the influenza virus circulation n for the period from october 2017 to may 2018 in some territories of Russia, collaborating with D. I. Ivanovsky Institute of Virology. The epidemic season had its own peculiarities: delayed and long-term activity of three influenza viruses, the share participation of which was almost equal, with some dominance of the influenza A(H1N1)pdm09 virus by the end of the season. Morbidity rates for the total population were comparable with the last epidemic season, meantime the morbidity among schoolchildren was higher. The number of hospitalizations and lethal outcomes was lower and mostly was found in patients of 65 years and older. In patients with severe acute respiratory infection (SARI) influenza A(H1N1)pdm09 was detected more frequently (58%). The influenza A(H1N1)pdm09 and A(H3N2) viruses were antigenically similar to strains included in influenza vaccines, at the same time, 96% of the isolated strains of influenza B virus belonged to a different evolutionary line. Epidemic strains were sensitive to neuraminidase inhibitors, except for 5 strains of influenza A(H1N1)pdm09 virus, isolated from pregnant women. Conclusions. The activity of non- influenza ARI viruses was similar to preliminary epidemic seasons. Recommendations on the influenza vaccines composition for the Northern hemisphere for 2019-2020 season are presented as well.

The article presents the features of the influenza virus circulation for the period from October 2016 to May 2017 in some territories of Russia collaborating with the D.I. Ivanovsky Institute of Virology, Federal State Budgetary Institution "N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology", Ministry of Health of the Russian Federation. One of the 2016-2017 season's peculiarities in Russia and countries of the Northern hemisphere was the earlier start of an increase in ARD morbidity with peak indexes reached towards the end of December 2016 - January 2017. First, influenza A(H3N2) virus was predominant; then, it was followed by influenza B virus activity observed until the end of the season. The indexes of morbidity were higher than in the previous season, while the rates of hospitalization and mortality were lower, lethal cases being detected in persons 65 years old and older. Epidemic strains of influenza A(H3N2) virus belonged to 3c.2a genetic group, reference strain A/Hong Hong/4408/2014, and its subgroup 3c.2a1, reference A/Bolzano/7/2016, that are antigenically similar. Strains of influenza B virus were antigenically similar to the B/Brisbane/60/2008 vaccine virus. Strains were sensitive to oseltamivir and zanamivir. The share participation of non-influenza ARI viruses was similar to preliminary epidemic seasons. WHO has issued recommendations for influenza virus vaccines composition for 2017-2018 for the Northern hemisphere.

The Epstein–Barr virus, which is persistent in the human organism throughout lifetime after the primary infection, is involved in the pathogenesis of a number of somatic chronic diseases. It is known that the virus successfully escapes the immune control, and has many mechanisms to regulate the components of immune system s as well. In our work, we summarized the current scientific data on the effect of the persistent Epstein-Barr virus on the function and quantity of T- and B-lymphocytes, NK cells, activity of the toll-like receptors, secretion of interleukins, interferons and other cytokines. The immunity dysfunction with the immunoactivation predominance leads to the formation of severe forms of chronic active Epstein–Barr virus infection such as the chronic mononucleosis, hemophagocytic lymphohistiocytosis. The immunosuppression is characteristic for the atypical course of the chronic active Epstein–Barr virus infection. The ability of some viral proteins to antigenic mimicry (that is, the homology of viral and human proteins) is the determining factor in the development of the chronic fatigue syndrome, multiple sclerosis and systemic lupus erythematosus. The Epstein–Barr virus is capable of the immortalization of the B-lymphocytes, including the autoaggressive ones, which leads to the formation of the chronic autoimmune diseases. Study of the development mechanisms of these diseases permits to develop the new, more effective, personalized prevention and treatment schemes, for example, using the targeting therapy.

The clinical and social impacts of persistent infections remain relevant. The main aspects of this pediatric problem are the epidemiology and pathogenesis of persistent infections, their clinical manifestations, possibilities for their treatment and prevention, and prediction of the active reproduction of infectious agents. The issues of the human body’s interaction of persistent viruses with viruses that cause acute infectious diseases remain inadequately studied. There is no answer to the question as to the nature of this (synergistic, competitive) interaction or lack thereof. It is unclear how the persistent viruses interact with the host genome. The family and interfamily types of persistent infections, which is of key value in infection prevention in not only a baby, but also in a fetus, have not been adequately explored. This paper focuses on the most important and interesting medical and biological aspects of the problem of persistent infections and gives answers to some of them.

In the 2015—2016 epidemic season, there were dominant influenza A(H1N1)pdm09 strains (over 90%) among the circulating influenza viruses in most countries of the Northern Hemisphere and in Russia. A study of the antigenic properties of influenza A(H1N1)pdm09 strains revealed no differences in those of vaccine virus. Sequencing showed that there were amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in the genes encoding internal proteins (PA, NP, M1, and NS1). The rise in the incidence in the Russian Federation, which was etiologically associated with influenza viruses, was registered in January-February 2016 with its maximum being observed at 4—5 weeks of 2016. Within the framework of the epidemiological surveillance of circulating influenza viruses in the Russian Federation, which was conducted by the WHO European Office, the D.I. Ivanovsky Institute of Virology, Honorary Academician N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology, Ministry of Health of Russia, and the Research Institute of Influenza, Ministry of Health of Russia, monitored at the Infectious Diseases Hospital One (IDH-1), Moscow Healthcare Department. Among 1491 examinees, influenza was verified in 104 (21.3%) adults, 208 (42.5%) pregnant women, and 177 (36.2%) children. Influenza A(H1N1)pdm09 was more often diagnosed in the age group of 15—40 years (63.7%); the proportion of influenza patients aged over 50 years increased (22.1%). Most adult patients had moderate influenza; pneumonia complicated the disease in 27.4%. Influenza in the pregnant women was complicated by pneumonia in 4.8% of cases. Influenza was more frequently diagnosed in infants and preschool children aged 0 to 3 years (42.9%), 4 to 6 years (41.2%), and older (15.9%), namely: 7—9 years (10%) and 10—12 years (5.9%). Influenza in the children was complicated by acute tonsillitis (19.4%) and varying degrees of laryngeal stenosis (12.4%). Bronchial obstructive syndrome developed in 2.5%, the rate of pneumonia was 6.2%. Antiviral therapy (AVT) in the early stages of the disease reduces the risk of its severity, the frequency of secondary complications, and the duration and degree of clinical symptoms of influenza. AVT with oseltamivir, zanamivir, imidazolyl ethanamide pentandioic acid (ingavirin), and interferon-a2b (viferon) has been performed in the patients hospitalized at Moscow IDH-1 in the 2015—2016 epidemic season.

The goal of this work was the evaluation of the frequency of human CMV infection among the women, whose pregnancy ended in miscarriage, detection of active forms of infection and treatment before pregnancy. Virological and sero-immunological techniques were used. A total of 116 women who had miscarriages before the 28 week of pregnancy were submitted to the CMV test. 109 women (94.0%) demonstrated positive results. 49 women (42.2%) had active form of the cytomegalovirus infection. 13 women (26.5%) had the recurrent form and 36 patients (73.5%) had the persistent form of CMV infection (stage of productive replication). All the women with active cMVi were treated before the next pregnancy. Immunomodulatory therapy for the treatment was used.