Kirill G. Krasnoslobodtsev

Introduction. Adenovirus infection occurs globally in the form of sporadic cases and isolated outbreaks. Human adenovirus type 55 (HAdV-55), endemic in China and South Korea, causes acute respiratory viral infections (ARVI) of varying severity, both among the civilian population and in military units in different countries of the world. Genomic research facilitates reliable identification of HAdV-55. The aim of this study was to identify HAdV isolated in Moscow in 2022, as well as to conduct whole-genome sequencing and comparative genomic research. Materials and methods. HAdV-55 was isolated from a sample of a patient hospitalized with pneumonia and analyzed using restriction fragment length polymorphism analysis and whole-genome sequencing. Bioinformatics comparative analysis was performed on a sample of sequences of 83 isolates. Results. The whole-genome sequencing of first isolated in Russia HAdV-55 was conducted. The sequence of isolate SCV3008:Ad55 was deposited in GenBank (Accession Number PQ641625). Unique mutations in the SCV3008:Ad55 genome were identified, one of which resulted in a conservative T29A substitution in the penton that did not affect its functions. Phylogenetic analysis showed clustering of SCV3008:Ad55 with isolates of clade II, which included representatives of 7 countries on different continents, indicating a wide distribution of HAdV-55. Isolates from endemic regions of China and South Korea formed separate clades. The study of microsatellite length polymorphism in untranslated regions of the genome became an additional tool for distinguishing closely related genomes. Conclusion. The obtained genomic information laid the foundation for further monitoring for HAdV-55 in Russia and demonstrated the informativeness and significance of whole-genome studies for monitoring adenoviruses. The development and implementation of genotyping methods aimed at detecting HAdV-55 and other clinically relevant genotypes will significantly improve the effectiveness of the diagnosis of adenovirus infections with the threat of developing bronchopneumonia.

The purpose of this work was to determine the characteristics of the circulation of acute respiratory viral infection (ARVI) pathogens during the epidemic season of 2023–2024 in the WHO regions and Russian Federation. Materials and methods. The article uses virological, immunological, and statistical methods, analytical material from the WHO website, to assess the circulation of ARVI pathogens in the Russian Federation and WHO regions. Results and discussion. The detection rate of positive samples in clinical materials was as follows: influenza viruses – 7.7%, ARVI – 17.1% and SARS-CoV-2 – 6.5%. According to antigenic and molecular genetic properties, the population of the dominant subtype of the influenza A(H3N2) virus was heterogeneous and differed from the vaccine strain. The favorable sensitivity profile of epidemic strains to drugs with antineuraminidase activity (oseltamivir and zanamivir) and cap-dependent endonuclease inhibitor (baloxavir marboxil) was preserved. There was a tendency to increase the activity of respiratory pathogens such as HPIV, HAdV, HRsV, HRV, HCoV and HMPV. WHO experts have developed recommendations on the composition of influenza vaccines for the countries of the Northern and the Southern hemispheres with the replacement of the component of the influenza A(H3N2) virus: A/Darwin/9/2021 with A/Thailand/8/2022 and А/Croatia/13601RV/2023 accordingly. Cases of human infection with avian and swine influenza viruses continue to be registered. Conclusion. Against the background of a relatively low circulation of new SARS-CoV-2 variants in the 2023-2024 season, epidemic activity of influenza viruses was recorded in the countries of the Northern hemisphere at the traditional time. Globally, its onset was associated with the influenza A(H3N2) virus, followed by an increase in the activity of the influenza A(H1N1) pdm09 virus and influenza B. As in previous seasons, differences in the proportion of influenza viruses in WHO regions, including cities of the Russian Federation, were traced.

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.

Ebola 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. A 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. Vaccinated 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). The 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. The study was funded by the Ministry of Health of Russian Federation; GamEvac-Combi ClinicalTrials.gov number, NCT03072030 , Pan African Clinical Trial Registry PACTR201702002053400.

Whooping cough does not lose its high importance in infectology. The combination of whooping cough with various viral infections can determine the nature of the disease and the development of complications. Of particular interest in modern conditions are the associations of whooping cough with viral agents, the significance of which has increased due to improved diagnostics in recent years. A clinical case of severe whooping cough in association with COVID-19 and rhinovirus infection in a child aged 1 month is presented. The clinical and laboratory dynamics of the disease and the features of pharmacological therapy are shown.

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.

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.

The main cause of death in patients with cystic fibrosis (CF) is infectious process in the lungs, in particular, chronic lung infections caused by various pathogens, most often a combination of bacteria, fungi, or viruses. Data on mixed bacterial and viral-bacterial infections from domestic and foreign sources are fragmentary and sparse. The dominant associations of bacterial and viral pathogens in patients with cystic fibrosis have not been studied properly, and data on their epidemiological significance are lacking. The aim of this study was to assess the prevalence of bacterial and viral infections in patients with cystic fibrosis and to substantiate the need for the development of virological monitoring. Methods. Biomaterials from the respiratory tract of CF patients (409 children and 160 adults with CF) examined from 2006 to 2022 were used. The study was carried out using bacteriological methods, molecular genetic methods (RT-PCR) and MALDI-TOF mass-spectrometry. Results. Microflora of the respiratory tract was shown to be mixed in 2/3 patients with CF. The microflora of the lungs of children with CF is a dynamic community of microorganisms with high diversity and variability. In adult patients, associations of microorganisms are more common than in children, but the composition of associations is less diverse. We isolated about 40 species of bacteria from adult patients and more than 85 species from children in our sample. NFMO prevailed, including Burkholderia cepacia complex, Pseudomonas aeruginosa, Achromobacter xylosoxidans, Achromobacter ruhlandii, Stenotrophomonas maltophilia, and Staphylococcus aureus, Candida albicans, Aspergillus spp. Real-time PCR showed the presence of rhinovirus RNA in 10% of samples obtained from children and 12.9% from adults with cystic fibrosis. Conclusion. Our results indicate the need for continuous monitoring of the lung microflora in patients with CF, including testing for viruses.

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.