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Introduction: The surveillance of influenza viruses in ARVI structure and study of their properties in epidemic season 2019-2020 in Russian Federation are actual for investigations due to tasks of Global Influenza Strategy initiated by WHO in 2019., Material and Methods: The data of epidemiological surveillance on influenza- and ARVI-associated morbidity and hospitalization in different age groups of population were analyzed; virological, genetic and statistical methods were used., Results: Preschool children were involved in epidemic the most. Meanwhile, the highest rate of hospitalization was observed in patients of 18-40 years old. Influenza A(H1N1)pdm09 virus dominated in etiology of ARVI in hospitalized patients and pneumonia. The role of respiratory viruses in severe cases of pneumonia and bronchoalveolar syndrome in children was shown. The differences in spectrum of circulating viruses caused ARVI in different regions of Russia were found. Influenza A(H1N1)pdm09 and B/Victoria-like viruses were the main etiological agents that caused of epidemic; its activity among all ARVI was 7.3 and 8.0%, respectively. The differences in antigenic properties of influenza A(H3N2) and B epidemic strains compared to vaccine viruses were found. The populations of epidemic strains were presented by following dominant genetic groups: 6B1.A5/183P for A(H1N1)pdm09, 3С.2а1b+137F for A(H3N2) and V1A.3 line B/Victoria-like for B viruses. The good profile of epidemic strains susceptibility to anti-neuraminidase inhibitors has been saved. The most of the studied influenza strains had the receptor specificity characteristic of human influenza viruses., Conclusions: Obtained results identified the peculiarities of viruses caused the influenza and ARVI in epidemic season 2019-2020 in different regions of Russia. These results suggested the important role of influenza A(H1N1) pdm09 in severe cases and pneumonia in adults 18-40 years old. The continuing drift in influenza viruses was found, which, apparently, could not but affect the efficacy of vaccine prophylaxis and was also considered in the recommendations of WHO experts on the composition of influenza vaccines for the countries of the Northern Hemisphere in the 2020-2021 season.

Introduction: The new reassortant of the swine flu virus A(H1N1)pdm09, which emerged in 2009, overcame the species barrier and caused the 2009-2010 pandemic. One of the key points required for the influenza virus to overcome the species barrier and adapt it to humans is its specific binding to the receptors on the epithelium of the human respiratory tract., Purpose: Studying the dynamics of changes in receptor specificity (RS) of the HA1 subunit of the hemagglutinin of the influenza A(H1N1)pdm09 virus strains isolated during the period 2009-2016 on the territory of the Russian Federation, and an analysis of the possible impact of these changes on the incidence rates of the population of the Russian Federation of pandemic influenza in certain epidemic seasons., Material and Methods: Standard methods of collecting clinical materials, isolation of influenza viruses, their typing and genome sequencing were used. For the study of RS of influenza A virus (H1N1)pdm09, the method of solid phase sialosidenzyme analysis was used., Results: It is shown that the change in the parameter W 3/6 , which characterizes the degree of a2-3 receptor specificity (a2-3-RS) of the influenza virus A(H1N1) pdm09 over a2-6-RS, coincides with the change in the incidence rates of the Russian Federation's pandemic flu in separate epidemic seasons. There is a tendency to increase the affinity of the virus A(H1N1)pdm09 to α2-3 analogs of the sialyl-glycan receptors of the human respiratory tract epithelium - α2-3-sialoglycopolymers (α2-3-SGP), and falls to α2-6-SGP, with the virus showing the greatest affinity for sulfated sialoglycopolymers., Discussion: Screening for RS strains of influenza A (H1N1)pdm09 virus isolated on the territory of the Russian Federation in 2009-2016 revealed a decrease in the affinity of viruses for a2-6-sialosides, especially for 6'SL-SGP, which is probably due to the presence of amino acid substitutions in the 222 and 223 positions of RBS HA1 viruses. Previous studies have shown that the presence of such substitutions correlates with an increase in the virulence of the influenza A virus (H1N1)pdm09 [16, 23]. Probably, the pandemic virus has evolved towards the selection of more virulent pneumotropic variants., Conclusion: Monitoring of the receptor specificity of a pandemic influenza virus makes it possible to identify strains with altered RS to the epithelium of the human respiratory tract and an increased ability to transfer from person to person. Change in the period 2009-2016 the W 3/6 parameter characterizing the degree of α2-3-RS excess of the influenza A(H1N1)pdm09 virus over α2-6-RS, coincides with the change in the incidence rates of the pandemic influenza population of the Russian Federation in certain epidemic seasons., Competing Interests: The authors declare no conflict of interest.

Comparative analysis of the three past epidemics with the participation of the pandemic influenza A(H1N1)pdm09 was conducted according to the results of the epidemiological trials of two WHO National influenza centers for the morbidity, hospitalization, and mortality of the influenza in 59 cities of Russia for the period from 2009 to 2013. The first wave of the pandemic of 2009 was the most severe. Compared with this wave, during the next epidemics of 2011 and 2013, the involvement of urban population in the epidemic was reduced, as well as the morbidity in the people 15-64 years old and schoolchildren 7-14 years old. The duration of the epidemic among the adult population, the mortality rate of the total population, and the mortality rates in all age groups were also decreased. Vice versa, the incidence in the children of preschool age and the elderly people and the duration of the epidemic among children (especially preschool children) were increased. The share of patients 65 years and older, children 0-2 years old, and patients with pathology of the cardiovascular systems among the deceased patients increased to 33.6%.

Aim: Determine the level of antibodies against socially significant types/serotypes of influenza virus in sera of individuals residing in various regions of Russia., Materials and Methods: 1525 samples of blood sera collected in August-December 2013 in 8 regions of Russian Federation were studied in hemagglutination inhibition reaction (HAI) with antigens obtained from A/California/07/09, (H1N1)pdm09, A/Victoria/361/2011(H3N2), B/Brisbane/60/2008 (Victoria line), B/Massachusetts/2/2012 (Yamagata line), A/Commongull/Chany/2006 (H5N1), A/Anhui/01/2013 (H7N9) influenza virus strains., Results: None of the blood sera samples had significant HAI titers against A/H5 and A/H7 antigens. Of all the 1525 samples, 788 (52%) were positive with A(H1N1)pdm09 antigen; 734 (48%) reacted with A(H3N2) antigen; 1010 (66%) samples were positive with B/Victoria antigen and 602 (39%) samples were positive with B/Yamagata antigen., Conclusion: Healthcare institutions should pay attention to the correction of population immunity profile in regions for the reduction of social-economic losses from seasonal influenza epidemics.

The peculiarities of the influenza viruses circulation in 2012-2013 are discussed. The results were obtained in 10 cities of Russia, where basic laboratories of the Influenza Ecology and Epidemics Center of on the basis of Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, are situated. The increasing rate of the ARD morbidity caused by influenza viruses was observed in January-March 2013. The highest indices of the morbidity were detected during 6-7 weeks with the following decreasing rate till threshold levels to week 14. The influenza A (H1N1) pdm09, A (H3N2), and B viruses were the cause of the epidemic, but their activity differed over areas of Russia. The results of study of the antigenic and genetic properties of the influenza strains demonstrated closed relatives with respect to vaccine strains. In addition, some heterogeneity of the circulating strains and their drift variants were found as well. All tested strains were sensitive to oseltamivir (excluding one A (H1N1) pdm09 strain), zanamivir, arbidol, and remained resistant to rimantadine. The ratio of the ARD viruses was comparable with the last epidemic seasons.

Aim: To characterize the 2013-2014 epidemic season from the results of detection of influenza infection in patients; to provide the molecular genetic characteristics of the strains isolated from deceased patients., Subjects and Methods: The investigators examined 1203 patients (387 children, 509 people older than 16 years of age, 307 pregnant women) admitted to Moscow Clinical Infectious Diseases Hospital One with the clinical signs of acute respiratory viral diseases. Nasal lavage and autopsy specimens were used to isolate viral strains, then to sequence genomic fragments, and to determine receptor specificity., Results: Out of the 1203 examinees, 284 (23.6%) were influenza-positive: 221 (77.8%), 24 (8.5%), and 39 (13.7%) patients had influenza A(H3N2), influenza A(H1N1)pdm09, and influenza B, respectively. Influenza was notified in 42,7% of the pregnant women. There was a preponderance of its moderate form; its severe form developed in single cases having comorbidities. One fatal outcome was registered. The intake of antiviral medications in the first 48 hours of the disease could prevent complications. The investigators revealed mutations in the strain isolated from the bronchoalveolar lavage fluid of a patient with severe pneumonia complicated by acute respiratory distress syndrome., Conclusion: There is evidence that there are mutant A(H1N1)pdm09 viruses that have high pneumotropicity. The high risk of their circulation in the population and the risk of severe influenza forms involving the lower respiratory tract remain. Early antiviral therapy in the first 36-48 hours diminishes the clinical manifestations of influenza and reduces the risk of developing complications.

The comparison of the first and second waves of the pandemic influenza A(H1N1)pdm09 in the world and Russia was performed on the basis of weekly reports of Regional offices for Europe and on the data of the Federal Center for Influenza on a weekly incidence of influenza and acute respiratory viral infections, hospitalization, and mortality from the influenza in the age groups of population in 49 cities of the Russian Federation. The first wave of the pandemic, which continued in the countries of the world all summer, was of mixed etiology and, in spite of the availability of imported cases, has not caused a steep increase in Russia. The second wave of the pandemic in the countries of the Southern hemisphere was less intense. In the countries of the Northern hemisphere (in autumn 2009), on the contrary, it was more intensive, which was associated with different seasonality of influenza in these hemispheres. In Russia, the second wave (2011) was of a lesser intensity as compared to the first with respect to the duration in the country and in urban areas, the incidence in the entire population, including schoolchildren and adults, the rate of hospitalization and case fatality rate reduction of laboratory-confirmed influenza infection. The duration of the last pandemic of 2009 was the same as in 1957 and 1968, and longer than in 1977. The morbidity was one-half less than in the pandemic of 1957 and 1968, and was approaching the pandemic 1977. At the same time, the incidence in children 3-6 and 7-14 years was higher than in previous pandemics.

Analysis of development influenza activity season 2010-2011 is presented. Significant participation of influenza A(H1N1)pdm09 virus and influenza B of Victoria lineage virus in the epidemic morbidity structure with minor participation ofA(H3N2) virus was revealed. The influenza viruses isolated in Russia according to antigenic properties were similar to the strains included in the vaccine composition. Drift variants of influenza A(H1N1)pdm09 viruses isolated in Astrakhan and St.-Petersburg were recognized using WHO CC in London as representatives of three new genetic groups.

The receptor specificity (RS) of pandemic influenza A(H1N1) pdm09 virus strains deposited into the State Collection of Viruses of the Russian Federation, D. I. Ivanovsky Research Institute of Virology, Ministry of Health and Social Development of Russia, in the 2009-2010 and 2010-2011 epidemic seasons to a panel of 9 sialoglycopolymers (SGP). The strains were divided into 3 groups according to the W(3/6) index proposed by the authors, which was equal to the amount of reactivities to unbranched alpha2-3-SGP to that of reactivities to unbranched alphal-6-SGP: W(3/6) < or = 1.0; 1.0 < W(3/6) < or = 1.5. The W(3/6) < or = 1.5 group showed a predominance of a2-3-RS, attended by the high incidence of fatal primary viral pneumonias (FPVP) (60.0%) and amino acid replacements in the HA1 receptor-binding site (RBS) (80.0%): D222{G, N} and Q223R. The 1.0 < W(3/6) < or = 1.5 group was characterized by mixed alpha2-3/alpha2-6-RS with the incidence of FPVP (29.7%) and amino acid replacements in the HA1 RBS (40.5%) (D222{G, N, V} and Q223), respectively. In the W(3/6) < or = 1.0 group, alpha2-6-RS was prevalent, FPVPs were absent and amino acid replacements in HA1 RBS (D222{G, E}) were seen only in 6.0% of cases. The number of strains with increased specificity to alpha2-3-sialosides increased in the 2010-2011 epidemic season as compared to the previous season. With their further spread among the population, there may be a rise in cases of severe primary viral pneumonias with possible fatal outcomes, which can be, however, accompanied by a decrease in the capacity of mutants to air-dropwise transmission.

Research Institute of Influenza, Ministry of Health and Social Development of Russia, Saint Petersburg The characteristics of the isolation of pandemic influenza A(H1N1)v viruses were studied on chick embryos (CE) and MDCK cell culture. The materials (nasal swabs and autopsies) were collected in different regions Russia in the period from 20 July to 30 December 2009. The paper gives the data of the antigenic analysis of isolates, their capacity to multiply in different species-specific and tissue cell cultures. The viruses isolated on CE were shown to have higher hemagglutination titers and to be more stable. Isolation from the autopsies was effective only on CE. All the test cell lines other than MDCK were insensitive to the isolated pandemic influenza strains. The antigenic analysis showed no significant antigenic drift of the viruses isolated during the first wave of the pandemic in the Russian Federation.

The paper describes dynamics, distribution and morbidity rate during the 2009 A(H1N1)v influenza epidemic in Russia. The epidemic appears to have been especially severe in the cities of the Far-East and Siberian Federal Districts where the average morbidity rate ranged from 6.4% to 19.2% (mean 10.3%) and the epidemic duration from 7.8 to 8 weeks. In less affected Southern and Central Federal Districts A(H1N1)v influenza occurred in 5.7% of the population. Schoolchildren aged 7-4 years showed the highest morbidity rate of 28.8%. The age group of 18-53 years accounted for 79.4% of the total lethality. Viral isolates were genetically stable and exhibited 98.9% hemagglutnin (HA) homology with reference viruses. None of the strains had an amino acid substitution at position 275 of neuraminidase (NA) responsible for resistance to oseltamivir. Towards the end of the epidemic, the viral population displayed a significant rise in the number of strains containing mutations in 4 genes (4 HA, 2 NA, 2 PB2 and 1 PA mutations respectively). 26.7% of the viral isolates obtained in the end of the epidemic had D222G substitution responsible for tropism of viruses to lung tissues. Epidemiologically, the 2009 A(H1NI)v influenza epidemic is described as moderate based on the absence of pathogenicity determinants typical of both A(H1N1) influenza virus of 1918 and A(H5N1) virus. The paper compares the 2009 epidemic with those caused by A/Honkong/68 and A/USSR/ 90/77 viruses. The necessity of classification for the discrimination between A(H1N1) subtype viruses is emphasized.

Aim: Assessment of genetic diversity of influenza virus A/H1N1 (sw2009) variants circulated in Russia, study of virus' pathogenicity in humans and potential resistance to antiviral drugs., Materials and Methods: Sequencing of PCR-fragments of genome of influenza viruses isolated from clinical and autopsy samples of 436 patients. Four full genome sequences of influenza viruses A/H1N1 (sw2009) were obtained. Phylogenetic analysis was performed., Results: High degree of homology (98.9-100%) was found among influenza A/H1N1(sw2009) viruses in HA and NA genes as well as in their aminoacid sequences (1.3 and 1.4% respectively). Differences in other proteins did not exceed 1.1%. Diversity was found in position 222 of receptor-binding locus of HA and single amino acid polymorphism--in several internal proteins. Known mutations determining resistance to Tamiflu and Arbidol were not detected. All viruses were resistant to remantadine. Molecular markers of high pathogenicity were not found., Conclusion: High homology of influenza viruses determines low level of antigenic differences although in populations of viruses there are variants with different levels of adaptation to human organism and different affinity to receptors of upper and lower respiratory tract that can determine their different transmissibility.

The paper gives the results of sequence analysis of 150 positive samples in real-time RT-PCR, including 47 autopsy materials from patients (including 10 pregnant women), who died from fatal pneumonia mainly in November-December 2009, in whom the lifetime etiological diagnosis had not been made and hence no early etiotropic therapy performed. 70% of the primary materials from the deceased patients were found to have pandemic influenza A(H1N1) v mutants in the lung tissue with D222G (15%), D222N (15%), D222E (2%) substitutions, as well as a mixture of mutants (38%). Nasopharyngeal lavages from 3 Chukotka deceased patients exhibited only consensus (nonmutant) D222 virus variants; there was a mixture of consensus and mutant virus variants in the trachea and a mixture of mutant ones in the lung. Preliminary data from the study of the interaction of the hemagglutinin of two strains having D222G and D222N mutations with 9 oligosaccharides imitating the variants of cell receptors for influenza A virus suggest that there is a double receptor specificity for alpha2'-3' and alpha2'-6'-sialosides with a preponderance of alpha2'-3'-specificity. Further spread of the mutants that have acquired a high virulence and preserved their capacity for the respiratory route of human infection may lead to the situation similar to that seen in the 1918-1919 pandemic. Another scenario for evolution of the virus is to preserve its receptor specificity for alpha2'-3'-sialosides and high virulence with losses of alpha2'-6' specificity and capacity for aerosol transmission, by damping the pandemic.