The aim of the study: to analyse diagnostic trends of HIV-infection in the Russian Federation in the period 2017–2022. Materials and methods. The study used data obtained from reports from the Federal Register of persons infected with the human immunodeficiency virus (FRHIV). The circumstances in HIV diagnosis and clinical and epidemiological characteristics of newly diagnosed patients, including CD4+ T-lymphocyte counts, were analysed. A likely time window between presumed infection and confirmation of HIV diagnosis was also determined. Categorical data evaluated in the study were presented as proportions and caparisoned using the chi-square test (χ2). In case of multiple comparisons, the Bonferroni correction for multiplicity was used. Quantitative data were tested for normality using the Kolmogorov-Smirnov criterion. In most cases, nonparametric characteristics of distributions — median and interquartile range — were applied, as well as the Mann-Whitney criteria for comparison of two independent groups and the Kraskell-Wallis criteria for comparison more than two groups, followed by pair wise comparisons using the Mann-Whitney criterion with Bonferroni multiplicity correction. A p-value<0.05 was considered statistically significant. Data analysis and graphical visualization was performed using the statistical software R version 4.1.1 and its libraries.Results and discussion. The results showed an increase in HIV detection through voluntary testing, preventive medical examination, and clinical indications. The proportion of injecting drug users (IDUs) decreased over time, while the involvement of women in the epidemic process and heterosexual transmission increased. Additionally, there was an increase in the proportion of patients aged 35 years and older. The analysis of CD4-cell counts revealed significant differences among gender and age subgroups. Women had higher absolute CD4-lymphocyte counts throughout the follow-up period. Patients aged 0–14 years had the highest proportion of CD4-lymphocytes over 500 cells/μL, while patients over 50 years old had the highest proportion of CD4-lymphocytes less than 200 cells/μL. Men who have sex with men and people infected through mother-to-child transmission had the highest mean baseline CD4-cell counts. IDUs and heterosexuals had a statistically significant decrease in CD4-cell counts over the follow-up period and also had the longest median time from infection to disease detection — 24 and 20 months, respectively.Conclusion: Thus, this study helps identify the most significant risk groups of HIV-infected individuals in Russia at present.
The aim of this work was to study the capacity of human T cells immune for SARS-CoV-2, to produce IFNγ, a marker of T cell immunity, in response to stimulation by a peptide pool in whole blood. Eighty samples of whole blood were received from the volunteers with known medical history in 2021, and 258 volunteers were examined in September-October 2022. In this study, 2 detection techniques were used, i.e.: (1) solid-phase enzyme immunoassay to determine antibodies of class G to RBD SARS-CoV-2; (2) IGRA test to determine IFNγ produced by antigen-specific lymphocytes in response to their stimulation by viral antigen. The parameters of the IGRA test were optimized with a sample of 80 specimens from the volunteers. The threshold value of the IFNγ level was determined (4.85 pg/mL), at the diagnostic specificity of 100% (80.6-100), and diagnostic sensitivity of 92.19% (83-96.6%), 95% CI. The study was further continued with a sample of 258 volunteers. Of them, 28.7%, did not exceed the threshold level of IFNγ after stimulation, according to results of the IGRA test. Meanwhile, all volunteers exhibited class G antibodies to RBB SARS-CoV-2. There was no correlation between the levels of antibodies and the level of interferon response in the entire group. When comparing IgG antibody levels and the amplitude of IFNγ (if exceeding the baseline level) in the groups differing in the time of the last vaccination, the median values of the parameters were slightly higher for the subgroup which was revaccinated 1-2 months before the study, while a significant difference between these subgroups was revealed only when evaluating IFNγ, pg/mL (Mann–Whitney criterion, p = 0.0321). According to the results of the study, it can be assumed that all the patients in the sample who were vaccinated and had COVID-19 infection, showed a humoral immune response. However, about a third of them lacked cellular immunity to SARS-CoV-2. There was no correlation between the levels of antibodies and the level of interferon response (Spearman’s criterion). Revaccination within previous 1-2 months has been shown to promote the increased amplitude of interferon response.
V nastoyashchee vremya adenovirusnye vektory shiroko ispol'zuyut v kachestve vakcinnyh i genoterapevticheskih preparatov blagodarya ih tekhnologichnosti i sposobnosti inducirovat' stojkij gumoral'nyj i kletochnyj immunnyj otvet. Odnako odni iz naibolee chasto ispol'zuemyh vektorov dlya razrabotki kandidatnyh vakcin — rekombinantnye adenovirusy cheloveka 5-go i 26-go serotipov (Ad5 i Ad26) stanovyatsya menee privlekatel'nymi iz-za vysokogo procenta naseleniya s immunitetom k dannym vektoram, vyzvannym vakcinaciej «Sputnikom V». Na segodnyashnij den' poyavlyaetsya tendenciya k vyboru al'ternativnyh serotipov adenovirusov v kachestve platform dlya razrabotki vakcin protiv novyh patogenov. Naprimer, adenovirus obez'yan 25-go serotipa (SAd25), prinadlezhashchij k podgruppe E, geneticheski otdalen ot Ad5 i proyavlyaet krajne nizkuyu seroprevalentnost' u lyudej, chto delaet ego privlekatel'nym al'ternativnym vakcinnym vektorom. Cel'yu raboty bylo sozdat' i issledovat' novuyu vakcinnuyu platformu na osnove adenovirusa obez'yan 25-go serotipa. Dlya konstruirovaniya i polucheniya rekombinantnyh adenovirusov ispol'zovali sovremennye molekulyarnobiologicheskie i virusologicheskie metody, dlya filogeneticheskogo analiza primenyali bioinformaticheskie metody. Poluchennyj rekombinantnyj adenovirusnyj vektor sposoben effektivno replicirovat'sya v proizvodstvennoj kul'ture kletok HEK293 (kletki pochki embriona cheloveka). Rezul'taty raboty obosnovyvayut celesoobraznost' dal'nejshego issledovaniya vektora SAd25 v kachestve platformy dlya razrabotki vakcin dlya profilaktiki razlichnyh infekcionnyh zabolevanij.
The demand for new treatment and prevention strategies of bacterial infections is increasing with the worldwide spread of acquired antimicrobial resistance among the microorganisms. This is especially important for healthcare-associated infections, exposed to a significant selective pressure of a closed system of in-patients organizations and pathogens' propensity to the resistance factors transmission. In this work, we assessed the in vitro potential of a new therapy approach against Gram-negative species based on combination of conventional antibiotics and a modified bacteriophage-derived endolysin LysECD7-SMAP, belonging to the class of enzybiotics. We have shown that such combinations can not only manifest a synergistic effect, but also restore the sensitivity of the microorganism to the antibiotic. The mechanism of the endolysins antimicrobial action suggests absence or low risks of development of bacterial resistance, which means that such a therapeutic regimen could be safe for course application. This study can serve as a basis for the development of new treatment regimens for patients with severe, recurrent or relapse infections caused by drug-resistant pathogens.
West Nile fever (WNF) is a viral infection caused by West Nile virus (WNV), a flavivirus of the Flaviviridae family. Virus circulates between mosquitoes and wild birds, but can infect other species, including humans. The first cases of West Nile fever were reported in Africa in the 1930s. Currently, WNV has a wide geographic range, which includes countries in Europe, Asia, Africa, Australia, and North and South America, where it periodically causes WNF outbreaks. The disease in human occurs with the development of fever, and in some cases ending up severe neurological complications. Studies of the virus in animal models demonstrate that virulence varies depending on the host species, the genotype of the virus, and the presence of substitutions in key viral proteins, even within the same genotype. These studies highlight the need for comparative studies of different WNV strains to evaluate the impact of amino acid substitutions on WNV pathogenesis. Analysis of key mutations and substitutions will allow the development of a safe and effective vaccine for the prevention of WNF.### Competing Interest StatementThe authors have declared no competing interest.
Technological versatility and the humoral and cellular immune response induction capacity have conditioned wide spread of adenoviral vectors as vaccine and gene therapy drugs. However, vaccination with Sputnik V made a significant portion of the population immune to the types 5 and 26 (Ad5 and Ad26) recombinant human adenovirus vectors, which are some of the most frequently used bases for candidate vaccines. Today, vaccine designers tend to select alternative adenovirus serotypes as platforms to develop vaccines against new pathogens on. A good example is simian adenovirus type 25 (SAd25), which belongs to subgroup E. It is genetically distant from Ad5 and exhibits extremely low seroprevalence in human beings, which makes it an appealing alternative vaccine vector. The purpose of this work was to design and study a new vaccine platform based on simian adenovirus type 25. We relied on the advanced methods of molecular biology and virology to construct and make recombinant adenoviruses; the phylogenetic analysis in the context of this study was enabled with bioinformatic methods. The resulting recombinant adenoviral vector can effectively replicate itself in the HEK293 cell line (human embryonic kidney cells). This work substantiates the expediency of further investigation into the SAd25 vector as a platform for development of the prevention vaccines against various infectious diseases.
Severe course of COVID-19 in inpatients can be caused by a number of reasons, including viral and bacterial superinfections. Empirical use of antibiotics, as well as poor infectious control stimulate the emergence and spread of multidrug-resistant bacteria. Klebsiella pneumoniae is the most common carbapenemase-producing bacterial pathogen causing nosocomial infections. These strains became significantly widespread during the COVID-19 pandemic. Objective. To analyze phenotypic and genetic characteristics of K. pneumoniae strains as the dominant bacterial pathogen in severe COVID-19 patients in the intensive care unit. Patients and methods. This study included 38 COVID-19 patients (including 6 patients with severe disease) treated in the intensive care units of Moscow and Saint Petersburg hospitals for infectious diseases between July 2020 and December 2020. All patients signed an informed consent to participate in the study; patient data was anonymized. The following samples were collected: sputum, bronchoalveolar lavage, and nasopharyngeal swabs. We performed bacteriological identification of isolated bacterial strains, drug susceptibility testing, and whole genome sequencing of K. pneumoniae strains. Results. The majority of K. pneumoniae strains isolated from patients with severe COVID-19 contained clusters of aerobactin and enterobacterin genes. However, some of them (strains 90 and 124) also contained clusters of yersiniabactin genes. These genes are associated with high virulence and ability to form biofilms. The isolated strains belonged to four sequence types (ST874, ST395, ST147, ST15) that are characterized by high virulence and antibiotic resistance. These K. pneumoniae strains can be considered as one of the major causes of severe and lethal COVID-19. Conclusion. Our findings suggest that the detection rate of K. pneumoniae in COVID-19 patients increased from 30% to 70% during the pandemic. Phenotypic tests demonstrated that more than 80% of the strains were resistant to most antibiotics used in patients with complicated COVID-19. The combination of gypervirulence and antibiotic resistance is crucial for nosocomial transmission of these strains and their effect on the disease outcome. The emergence of hyper-resistant pathogens necessitates regular epidemiological monitoring and robust infection control in Russian hospitals, especially in intensive care units. Key words: COVID-19, severe disease, Klebsiella pneumoniae, genome sequencing, carbapenemases, hypervirulence, antibiotic resistance
COVID-19 vaccination campaign has been launched around the world. More than 8 billion vaccines doses have been administered, according to the WHO. Published studies shows that vaccination reduces the number of COVID-19 cases and dramatically reduces COVID-19-associated hospitalizations and deaths worldwide. In turn, the emergence of SARS-CoV-2 variants of concern (VOC) with mutations in the receptor-binding domain (RBD) of S glycoprotein poses risks of diminishing the effectiveness of the vaccination campaign. In November 2021, the first information appeared about a new variant of the SARS-CoV-2 virus, which was named Omicron. The Omicron variant is of concern because it contains a large number of mutations, especially in the S glycoprotein (16 mutation in RBD), which could be associated with resistance to neutralizing antibodies (NtAB) and significantly reduce the effectiveness of COVID-19 vaccines. Neutralizing antibodies are one of the important parameters characterizing the protective properties of a vaccine. We conducted a study of neutralizing antibodies in the blood serum of people vaccinated with Sputnik V, as well as those revaccinated with Sputnik Light after Sputnik V. Results showed that a decrease in the level of neutralizing antibodies was observed against SARS-CoV-2 Omicron (B.1.1.529) variant in comparison to B.1.1.1 variant. Analysis of the sera of individuals vaccinated with Sputnik V 6-12 months ago showed that there was a decrease in the level of neutralizing antibodies by 11.76 folds. While no direct comparison with other vaccines declines has been done in this study, we note their reported decline in antibody neutralization at a much more significant level of 40-84 times. At the same time, the analysis of sera of individuals who were vaccinated with Sputnik V, and then revaccinated Sputnik Light, showed that 2-3 months after revaccination the decrease in the level of neutralizing antibodies against the Omicron variant was 7.13 folds. Despite the decrease in NtAb, we showed that all revaccinated individuals had NtAb to Omicron variant. Moreover, the NtAb level to Omicron variant in revaccinated sera are slightly higher than NtAb to B.1.1.1 in vaccinated sera.
Высокая плотность населения в городах с хорошо развитыми транспортными путями сообщения и туризмом может привести к распространению вирусных инфекций по всему миру в считаные дни. Новый коронавирус SARS-CoV-2 стал причиной заболевания COVID-19 уже более 2 000 000 человек и унес жизни более 156 000 человек по всему миру. Одной из основных причин такого стремительного развития пандемии послужило отсутствие диагностических тест-систем для выявления SARS-CoV-2. Применение молекулярно-биологических методов дает возможность быстро обнаруживать РНК вируса SARS-CoV-2 в клинических образцах, что позволяет уточнять диагноз у пациентов с тяжелыми формами течения болезни, а также выявлять людей с бессимптомным течением заболевания или находящихся в инкубационном периоде. Наиболее доступным, высокочувствительным и специфичным методом идентификации НК SARS-CoV-2 в биологических образцах является ПЦР с гибридизационно-флуоресцентной детекцией сигнала в режиме реального времени (ПЦР-РВ). Текущая вспышка COVID-19 в России требует наличия как можно большего количества ПЦР-РВ- тест-систем для проведения масштабных скрининговых исследований с целью выявления инфицированных лиц, своевременное выявление которых является крайне важным условием успешного предотвращения распространения вируса.
Testing the surrounding environment for the presence of biogenic aerosols is crucial in ensuring its safety for the population.It is often necessary to collect aerosol samples from large areas in short time, which demands excellent particle collection efficiency, a sufficient incoming air flow rate and a capacity to maintain the viability of the collected samples.Below we present the aerosol sampler with a high volumetric flow rate based on a two-stage particle concentration algorithm and consisting of a virtual impactor and a cyclone concentrator with a recirculating liquid phase.We provide all necessary calculations and an algorithm for modeling impactor parameters.The sampler was tested using dry and liquid formulations dispersed into the particles of 0.5 to 5 µm in diameter.We demonstrate that at volumetric flow rates over 4,000 l/min efficiency of particle collection into the liquid phase at a volume of 10 ml makes over 20% of the total aerosol mass and at volumetric flow rates over 300 l/min this value is over 60%.The proposed device maintains viability of the collected microorganisms.The sampler is portable, with flexible settings for sampling and cleaning, and can be controlled remotely over the network.Обнаружение биогенных аэрозолей является важной задачей при обеспечении безопасности жизнедеятельности человека в современных условиях.На практике часто требуется собирать аэрозоли с больших площадей за малый промежуток времени, что накладывает жесткие ограничения на эффективность пробоотбора, величину прокачиваемого в единицу времени объема воздуха и жизнеспособность собранного биоматериала.В работе представлены результаты по разработке и испытанию устройства отбора аэрозольных проб с высокой объемной скоростью и двухступенчатым концентрированием аэрозольных частиц -виртуального импактора и циклонного коллектора с рециркулирующей жидкой фазой.Приведены алгоритм и результаты расчета параметров импактора, результаты испытаний устройства на модельных сухих и жидких тест-препаратах для частиц размерами 0,5-5 мкм.Подтверждено, что при объемных скоростях пробоотбора выше 4000 л/мин эффективность отбора в жидкую фазу объемом до