INTRODUCTION:Predisposition to different courses of the infectious process is largely associated with the polymorphisms in human genome, especially in genes encoding proteins of the immune system. In the early stages of influenza infection such components of innate immunity as interferons I (α/β) and III (λ) type play a significant role in limiting virus replication. The aim of the work was to investigate associations of single nucleotide polymorphism in IFNL3 (rs8099917 T/G) and IFNL4 (rs12979860 C/T) genes with different course of influenza, and identify genetic markers of influenza complicated by community-acquired pneumonia. The genes noted above affect the production of interferon-λ3, which is involved in restriction of the viral replication. MATERIALS AND METHODS:Samples from 456 patients with mild (n = 150), moderate (n = 173), and severe (n = 133) influenza were studied. The viral RNA was detected by reverse transcription and polymerase chain reaction (RT-PCR). Polymorphisms in IFNL3 (rs8099917 T/G) and IFNL4 (rs12979860 C/T) genes was detected by PCR. Statistical analysis was performed using SNPStats software. RESULTS:Patients with the C/T or T/T genotype of IFNL4 gene (rs12979860 C/T) were more likely to have pneumonia than those with the C/C genotype (OR 2.47 (1.31-4.63); p = 0.0044; q = 0.0059). The presence of one T allele increased the risk of developing pneumonia (OR 2.02 (1.05-4.02); p = 0.006; q = 0.008). In the presence of the T/T genotype, the risk increased more than twofold: OR 2.14 (1.31-3.48). Analysis of the SNP of IFNL3 gene (rs8099917 T/G) revealed a weak association of the G allele with pneumonia (OR 1.86 (1.04-3.31); p = 0.03; q = 0.045). CONCLUSION:Genetic markers of increased risk of community-acquired pneumonia in influenza include the presence of the T allele in IFNL4 gene (rs12979860 C/T) and, to a lesser extent, the G allele in IFNL3 gene (rs8099917 T/G). Patients carrying these alleles have an increased risk of developing pneumonia, especially in old age.

The purpose of this work was to determine the characteristics of the circulation of various viral respiratory pathogens during the epidemic season 2022–2023 against the background of the ongoing evolutionary variability of SARS-CoV-2. Materials and methods. The article uses methods used in «traditional» and «hospital» epidemiological surveillance of acute respiratory viral infections. Results and discussion. The period from October 2022 to September 2023 was characterized by early and high activity of influenza A(H1N1)pdm09 virus, which was replaced by influenza B virus. The antigenic and genetic properties of strains were closely related to influenza vaccines viruses recommended by WHO experts for the current season. The effectiveness of influenza vaccines was confirmed (75.0%). All of the studied influenza A(H1N1)pdm09, A(H3N2) and B epidemic strais retained sensitivity to drugs with antineuraminidase activity. The structure and share of other ARVI pathogens have changed somewhat compared to the previous season: There was a tendency to increase the activity of HAdV and HMPV; almost equivalent activity of HRsV, HRV, HCoV and HBoV; and a decrease in HPIV activity. At the same time, the frequency of other ARVI pathogens did not reach the indicators of the pre-pandemic COVID-19 period. The rationale for updating the composition of influenza vaccines for the countries of the Northern Hemisphere in the 2023–2024 season is given.

Aim. The study of metapneumovirus infection clinical and immunological features in children of different ages. Patients and methods. An analysis of 22 patients with mono-metapneumovirus infection is presented. There were 7 (31.8%) children under the age of 1 year, 8 (36.4%) — 1—3 years old, 7 (31.8%) — 4—7 years old. Diagnosis of metapneumovirus infection was based on clinical data and on PCR analysis of nasopharyngeal mucus. Immunological studies in 10 patients included immunophenotype of patient's blood lymphocytes and analysis of the interferon system. Results. Among children under the age of 1 year 71.4 ± 17.1% were diagnosed with obstructive bronchitis and 28.6 ± 17.1% had pneumonia. In patients aged 1—3 years pneumonia was observed more often (55.6 ± 17.6%), obstructive bronchitis — less often (33.3 ± 16.7%), and in 11.1 ± 11.1% bronchitis occurred without symptoms of bronchial obstruction. In children aged 4—7 years only the upper respiratory tract was affected in 14.3 ± 13.2% of cases, 57.1 ± 18.7% developed bronchitis and 28.6 ± 17.1% — pneumonia. The immune system state was characterized by a low content of T-helpers (CD3 + CD4 + ) and NK-cells (CD3-CD16 + CD56 + ) detected in 7 (70%) and 5 (50%) patients respectively. IFNγ production was reduced in 70% of children and IFNα in 80%. Conclusion. Metapneumovirus infection in children in modern conditions is characterized by the frequent development of inflammatory changes in the bronchopulmonary system in the early stages of the disease. The disease severity was due to both manifestations of respiratory failure and severe symptoms of intoxication. Immunological studies revealed changes in the cellular link and the interferon system in all age groups.

The purpose of the work was to investigate the association of individual allelic variants of the polymorphic loci of genes IFNL3 (rs8099917 T/G) and IFNL4 (rs12979860 C/T) with the se-verity of COVID-19. No reliable association was found between individual allelic variants and T/G or C/T alleles of these loci of IFNL3 and IFNL4 with the severity of COVID-19 in residents of the Moscow region.

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.

Acute respiratory viral infections remain the most common diseases in the world, accounting for about 90% of all infectious diseases. The possibilities of etiological decoding of ARVI using modern examination methods made it possible to establish an increase in the proportion of rhinovirus infection in the structure of ARVI.The aim of the study in this regard was to study the features of the clinical course of rhinovirus infection in children of different ages in modern conditions. The study included 50 patients with rhinovirus infection of children, among whom 1 2 children (24%) were under 1 year old; 34 children (68%) — 1—3 years old, 4 children (8%) — 3—7 years old. To confirm rhinovirus infection, a study of mucus from the nasopharynx by PCR was carried out.A thorough analysis of the symptom complex of the infection showed that in 1 3 (26%) patients the infectious process was limited to lesions of the upper respiratory tract, in 14 (28%) there were symptoms of acute stenosinglaryngotracheitis, in 1 1 (22%) children developed pneumonia, in 1 2 (24%) — bronchitis, with obstructive syndrome in 1 0 (83.3%) patients in this group.

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 World Health Organization (WHO) searches influenza virus circulation in community and in natural biocenosis, studies virus strains and their properties, develops diagnostic methods and preventive measures since 1940 th worldwide because of epidemic actuality and high pandemic potential of the influenza virus. The Federal Influenza Center (including Federal Research Institute of Influenza, Saint-Petersburg, and the Center of Virus Ecology, D.I.Ivanovskiy Virology Institute, Honorary Academician N.F.Gamaleya Federal Research Center of Epidemiology and Microbiology, Federal Research Center for Epidemiology and Microbiology, Moscow) performs similar work in Russia in close cooperation with WHO within the framework of the International Programme of Influenza Monitoring. A(H1N1)pdm09 influenza virus dominated in the Northern Hemisphere in the 2015 – 2016 epidemic season. Morbidity growth was noted from the end of January, 2016, to the beginning of March, 2016. The peak morbidity at the 5th week of the year exceeded the epidemic threshold (132 cases per 10,000 of population) and morbidity in the 2014 – 2015 season significantly and approached to the peak morbidity of the 2009 – 2010 epidemic season. The epidemic growth in Russian Federation was provided by three influenza viruses: A(H1N1)pdm09, В and A (H3N2). A(H1N1)pdm09 virus caused 18% of all acute respiratory diseases and accounted for 84% of circulating influenza viruses. Flu was diagnosed in patients of different age with maximal frequency in 3- to 6-year old children. Peak admission number was registered at 5 and 6 weeks (3,538 and 4,109 cases, respectively); this number exceeded the similar parameter of the 2009 – 2010 season. Patients of 15 to 64 years old were admitted more often including those with acute respiratory infection. Two hundred and thirty nine deaths were registered to the 5 th of April, 2016, according to data from the Federal Influenza Center and the Center of Virus Ecology. The diagnosis of A(H1N1)pdm09 flu was confirmed in 97.9% of deaths. Molecular analysis of isolated strains of A(H1N1)pdm09 influenza virus revealed amino acid substitutions in receptor binding site and SA site of hemagglutinin and in genes coding intrinsic proteins PA, NP, M1, and NS1. Influenza virus strains resistive to anti-neuraminidase drugs were encountered in #< 1% in the Northern Hemisphere countries. No strains studied were sensitive to adamantine derivates.

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.

A prospective, two-center, open-label, randomised clinical trial assessing the efficacy and tolerability of treatment strategies involving the administration of Ergoferon and Kagocel in paediatric outpatients aged over 3 years was carried out. The study was conducted with the objective of obtaining a comprehensive evaluation of drug-based therapy options used in routine paediatric practice to treat acute respiratory infections (ARI) during the 2012-2013 epidemic season. A total of 90 ARI-diagnosed child-age patients able to initiate treatment within 48 hours of infection onset entered the trial. Nine participants were excluded from final analysis due to protocol violation. The patients were randomised into 2 groups (Ergoferon (group 1): 41 subjects and Kagocel (group 2): 40 subjects) with similar distribution of sex, age, baseline clinical data, and time of treatment initiation. The study involved clinical assessment including daily body temperature monitoring (morning/evening measurements) and three PCR assays of nasal swabs. At visits 2 and 3, the number of patients achieving normal body temperature (primary endpoint) was estimated and severity of intoxication and catarrhal syndromes and individual symptoms as well as the rate of virus elimination were evaluated. In addition, visit 3 included the assessment of the volume and cost of treatment in conjunction with clinical benefit and treatment safety/tolerability (as judged by the physicians and parents). By the end of the first day of treatment, the number of children with body temperature of above 38 C was significantly decreased as compared to the morning baseline (p=0.008) and respective values in group 2 (p=0.02). At visit 2 (treatment day 4), the state of 80% of patients in either group was assessed as satisfactory and over 70%, respectively, could maintain normal body temperature throughout the day. Total intoxication scores were reduced by 7-10 points and were less than 9 in 100% of patients. The overall scores of catarrhal symptoms were 2.5-3 points lower than the baseline levels and were less or equal to 9 in 80-90% of children in either group. By visit 3, 'satisfactory' health assessments were reported for 95% of patients in respective groups. Signs of catarrh were completely resolved in 37% of participants in group 1 and 15% in group 2 (p=0.03). At the same point, 66% of patients in group 1 and 55% in group 2 were observed to have no (or isolated or negligible) signs of infection which did not require continuation of treatment (p>0.05). The percentage of children achieving recovery was 3 times greater in group 1 than in group 2 (p=0.01). No bacterial complications were presented by any of the study subjects. The severity of individual symptoms of catarrh varied significantly between the groups as observed at visits-2 and 3. At visit 2, 92% of subjects in group 1 had no or only minor (requiring no drug intervention) obstruction breathing through the nose and 26.8% reported no nasal blockage (p=0.04), while the latter was observed to persist in 60% of children in group 2 (p<0.001). By the time of visit 2, the number of patients attaining complete resolution of serous nasal discharge was increased by more than 2.5 in group 1 - up to 31.7% (p=0.01), while this number in group 2 was 17.5% and did not significantly differ from the baseline level (visit 1, p=0.4). There were also differences in cough pattern changes between the groups, i.e. the dry cough was converted into a productive cough in 44% of subjects in group 1 vs. 20% in group 2 (p=0.06). As reported at visit 3, the number of patients having no difficulty breathing nasally was 88% in group 1 vs. 38% in group 2 (p=0.008). The percentage of children exhibiting complete resolution of cough as observed at visit 3 was 2 times higher in group 1 then in group 2 (respectively, 24% vs.12%; p>0.05). No adverse events related to medications used as part of the treatments administered were reported during the study. The mean CGI scores (overall safety and efficacy index) were similar between the groups: 3.5±0.6 in group 1 vs. 3.3±0.6 in group 2 (p=0.25). The percent of maximum scores was 51% and 38% in groups 1 and 2, respectively. Mean efficacy scores in patient groups were 3.9±0.6 and 3.6±0.6, respectively (p=0,036), with respective tolerability ratings represented by scores of 4.3±0.7 and 3.8±0.5 (p=0,002). The mean number of drugs prescribed was 4.7±1.0 in group 1 vs. 6.0±1.3 in group 2 (p<0.001). The percent of cases where not more than 4 medications were administered to a subject and the number of occasions when a child was prescribed to receive 6 drugs or over varied significantly between the groups and were 46% vs.10% and 27% vs. 70% , respectively (p<0.001). Similarly, there were differences in the duration of treatment with drugs belonging to distinct pharmacological groups: 6.0±1.4 vs.8.8±1.5 days (p<0.05) for antihistamines; 6.1±2.0 vs. 7.1±2.4 days (p=0.15) for decongestants; 6.0±1.1 vs.7.1±2.4 days (p=0.07) for mucolytics; and 6.9±1.4 vs. 8.4±2.3 days (p=0.04) for locally-acting anti-inflammatory and antiseptic agents, as reported for group 1 vs. group 2, respectively. The mean treatment cost per ARI case was 1353±320.2 rubles in group 1 compared to 1768±491.0 rubles in group 2 (p=0.008). Swab specimens from 76 children (41 subjects from groupl and 35 from group 2) were tested using PCR. Baseline specimens were mostly positive for rhinoviruses, influenza A(H3N2) virus, and parainfluenza virus types 2 and 3. By visit 2, virus elimination was demonstrated for 46% of cases in group 1 and 23% in group 2 (p<0.03). By the time of visit 3, the tests were indicative of virus removal for 66% of children in group 1 and 49% in group 2. Thus the antiviral drugs used as part of combination treatment of ARIs were shown to enable fast recovery and prevent the development of bacterial complications, proving to be well-tolerated. Patients in the Ergoferon group demonstrated faster resolution of ARI symptoms and shorter elimination of respiratory viruses, had less need for additional medications, and.required 23% less spending on treatment, resulting in a greater number of favorable assessments of.Ergoferon by both the physicians and parents.

The aim of this study was to monitor in-hospital influenza virus infection during 2015 – 2016 epidemic flu season. Methods. Influenza virus was searched in patients hospitalized to a clinical infectious diseases hospital with acute respiratory viral infection during 2015 – 2016 influenza seasonal growth period using real-time RT-PCR method. Influenza virus was isolated from nasal swabs and autopsy material using canine kidney cell line. Other laboratory methods used included complete blood count, blood chemistry, blood gas analysis, urinalysis, and chest X-ray examination. Results. We examined 1,491 patients (375 adults, 546 children, 570 pregnant women with early gestational age). The proportion of hospitalized patients with confirmed A / H1N1pdm09 influenza in January – February, 2016, was 91.3%. A / H3N2 influenza virus was diagnosed in 5.7%, influenza B virus was isolated in 1.2% of patients. Totally, influenza virus was detected in 35.2% of samples, of which 30.1% of samples were obtained from adults, 33.7% of samples were obtained from children, and 39.8% of samples were obtained from pregnant women. The prevalent patient’s age was 15 to 60 years (76.1%) in adults and 3 to 6 years in children. Moderate course of influenza with a high rate of hospital admission was seen more often and was similar to that of 2009 – 2010 epidemic season. Proportion of patients with flu complicated by pneumonia was higher than that in 2014 – 2015 epidemic season. Bilateral lung injury was diagnosed in 48.4% of patients. High mortality in ICU (46.4%) was due to delayed start of antiviral treatment and late admission to a hospital. Conclusion. In 2015 – 2016 epidemic flu season, higher morbidity, complications and poor outcomes were related to predominant infection of A – H1N1pdm09 influenza virus. Risk factors of complications and death were delayed care seeking, lack of modern antiviral medications and comorbidity.

This work describes the specific features of the influenza virus circulating in the period from October 2015 to March 2016 in 10 cities of Russia, the basic laboratories of CEEI at the D.I. Ivanovsky Institute of Virology "Federal Research Centre of Epidemilogy and Microbiology named after the honorary academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation. The increase in the morbidity caused by influenza viruses was detected in January-February 2016. The duration of the morbidity peak was 4-5 weeks. The most vulnerable group included children at the age from 3 to 6; a high rate of hospitalization was also detected among people at the age of 15-64 (65%). In clinic symptoms there were middle and severe forms with high frequency of hospitalization as compared with the season of 2009-2010, but much higher in comparison with the season of 2014-2015. Some of the hospitalized patients had virus pneumonias, half of which were bilateral. Among these patients, 10% were children; 30%, adults. The mortality in the intensive care unit of the hospital was 46%. Almost all lethal cases were among unvaccinated patients in the case of late hospitalization and without early antiviral therapy. The predominance of the influenza A(H1N1)09pdm virus both in the Russian Federation and the major part of the countries in the Northern hemisphere was noted. The results of the study of the antigenic properties of influenza strains of A(H1N1)pdm09 virus did not reveal any differences with respect to the vaccine virus. The sequencing data showed the amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in genes encoding internal proteins (PA, NP, M1, NS1). Strains were sensitive to oseltamivir and zanamivir and maintained resistance to rimantadine. The participation of non-influenza ARI viruses was comparable to that in preliminary epidemic seasons.

A randomized double-blind controlled study was carried out to evaluate changes in the clinical presentation of acute obstructive bronchitis in preschool children using antiviral, anti-inflammatory therapy. The study enrolled 54 subjects'(aged 3-6 years old) hospitalized with verified diagnosis of acute obstructive bronchitis. Their parents had given their informed consent for participation. Group 1 (n=26) received etiotropic therapy with the drug having complex antiviral, anti-inflammatory and antihistamine effect (Ergoferon), group 2 (n=28) received placebo. Meanwhile all children received complex therapy of ARI. To evaluate therapeutic efficacy the following parameters were compared: time to elimination of the clinical manifestations of the disease; extent of alleviation of the key symptoms, incidence of wheezing episodes and complications.RESULTS:According to PCR, rhinoviruses prevailed in both groups in oropharyngeal swabs (31% in.group 1 and 57% in group 2); furthermore, RNA of influenza B virus, respiratory syncytial virus, parainfluenza virus types 2 and 4 and metapneumovirus were also detected; 3 children in each group simultaneously had RNA of various viruses; no differences between the groups were observed. In group 1 average duration of increased body temperature (morning measurement) was 1.6 (1.4-1.9)±0.6 days, respectively, and all children reached normal values of morning and evening body temperature by the end of 3-day therapy. In group 2 morning body temperature reached normal values on types 2.7 (2.1-3.3)±1.2 days, respectively (U-test, P==0.002), while complete normalization in all children took place on day 6 of the follow-up. Area under curve for daily body temperature was statistically lower in group 1: 514.3 (513.8-514.9)±1.4 ('C X days) vs. 516.3 (515.1-517.5)±2.5(*C X days) in group 2 (U-test, P=0.002). Intoxication in group 1 was eliminated within 2.8 (2.5-3.1)±0.80 days on average, in group 2 - within 4.5 (4.1-4.8)±0.96 days (P<0.001). Intensity of catarrhal symptoms (nasal congestion, rhinitis, cough) resolved faster in group 1 (P<0.05). Average elimination term for catarrhal symptoms was 6.0 (5.7-6.3)±0.8 days vs. 9.0 days for groups 1 and 2 (P<0.001), respectively. Wheezing resolved within 4.1 (4.0-4.2)±0.3 days on average in group 1 and within 6.9 (6.7-7.0)±0.4 days in group 2 (P<0.001). Despite the treatment, eight children in group 2 showed moderate reinforcement of wheezing within the first 3-4 days of therapy, 3 of them had body temperature increased to subfebrile values requiring antibacterial treatment. Neither of children in group 1 had any bacterial complications or reinforced wheezing. All children from group 1 had complete recovery on day 8. Neither of subjects recovered completely on day 9 in group 2. Average recovery term in group 1 was 6.0 (5.7- 6.3)±0.8 days vs. 9.0 days in group 2 (P<0.001). No adverse effects associated with the medicinal products were recorded during the study. Average rating of therapeutic efficacy by the investigator using CGI scale was 3.7 (3.5-3.8)±0.49 scores in group 1 vs. 2.6 (2.3-2.9)±0.69 scores in group 2 (P<0.005). Rating of wheezing therapy efficacy was similar: 3.7 (3.4- 3.9)±0.57 and 2.2 (1.7-2.7)±1.29 for groups 1 and 2, respectively. Safety of the products according to CGI scale reached maximum in both groups. Parents' rating of the treatment in group 1 was 50% higher as compared to group 2: 3.6 (3.4- 3.8)±0.57 scores and-2.5 (1.8-2.9)±1.31 scores (P<0.005).CONCLUSION:Ergoferon in complex therapy of acute obstructive bronchitis in preschool children ensures rapid therapeutic effect including elimination of wheezing symptoms, prevention of bacterial complications, wheezing progression and is well tolerated by the subjects.

The World Health Organization (WHO) searches influenza virus circulation in community and in natural biocenosis, studies virus strains and their properties, develops diagnostic methods and preventive measures since 1940 th worldwide because of epidemic actuality and high pandemic potential of the influenza virus. The Federal Influenza Center (including Federal Research Institute of Influenza, Saint-Petersburg, and the Center of Virus Ecology, D.I.Ivanovskiy Virology Institute, Honorary Academician N.F.Gamaleya Federal Research Center of Epidemiology and Microbiology, Federal Research Center for Epidemiology and Microbiology, Moscow) performs similar work in Russia in close cooperation with WHO within the framework of the International Programme of Influenza Monitoring. A(H1N1)pdm09 influenza virus dominated in the Northern Hemisphere in the 2015 – 2016 epidemic season. Morbidity growth was noted from the end of January, 2016, to the beginning of March, 2016. The peak morbidity at the 5th week of the year exceeded the epidemic threshold (132 cases per 10,000 of population) and morbidity in the 2014 – 2015 season significantly and approached to the peak morbidity of the 2009 – 2010 epidemic season. The epidemic growth in Russian Federation was provided by three influenza viruses: A(H1N1)pdm09, В and A (H3N2). A(H1N1)pdm09 virus caused 18% of all acute respiratory diseases and accounted for 84% of circulating influenza viruses. Flu was diagnosed in patients of different age with maximal frequency in 3- to 6-year old children. Peak admission number was registered at 5 and 6 weeks (3,538 and 4,109 cases, respectively); this number exceeded the similar parameter of the 2009 – 2010 season. Patients of 15 to 64 years old were admitted more often including those with acute respiratory infection. Two hundred and thirty nine deaths were registered to the 5 th of April, 2016, according to data from the Federal Influenza Center and the Center of Virus Ecology. The diagnosis of A(H1N1)pdm09 flu was confirmed in 97.9% of deaths. Molecular analysis of isolated strains of A(H1N1)pdm09 influenza virus revealed amino acid substitutions in receptor binding site and SA site of hemagglutinin and in genes coding intrinsic proteins PA, NP, M1, and NS1. Influenza virus strains resistive to anti-neuraminidase drugs were encountered in #< 1% in the Northern Hemisphere countries. No strains studied were sensitive to adamantine derivates.