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Introduction. Since the outbreak of the COVID-19 pandemic caused by SARS-CoV-2 novel coronavirus, the international community has been concerned about the emergence of mutations altering some biological properties of the pathogen like increasing its infectivity or virulence. Particularly, since the end of 2020, several variants of concern have been identified around the world, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). However, the existing mechanism of detecting important mutations are not always effective enough, since only a relatively small part of all pathogen samples can be examined by whole genome sequencing due to its high cost.Material and methods. In this study, we have designed special primer panel and used it for targeted highthroughput sequencing of several significant S-gene (spike) regions of SARS-CoV-2. The Illumina platform averaged approximately 50,000 paired-end reads with a length of ≥150 bp per sample. This method was used to examine 579 random samples obtained from COVID-19 patients in Moscow and the Moscow region from February to June 2021.Results. This study demonstrated the dynamics of distribution of several SARS-CoV-2 strains and its some single mutations. It was found that the Delta strain appeared in the region in May 2021, and became prevalent in June, partially displacing other strains.Discussion. The obtained results provide an opportunity to assign the viral samples to one of the strains, including the previously mentioned in time- and cost-effective manner. The approach can be used for standardization of the procedure of searching for mutations in individual regions of the SARS-CoV-2 genome. It allows to get a more detailed data about the epidemiological situation in a region.

At present it is impossible to develop epidemiologic surveillance and control over any infection regarding studies on dynamics of morbidity, seasonality and periodicity without using mathematical modeling techniques. Our research goal was to study regularities in manifestations of epidemic process for enterovirus (non-polio) infection (EVnI) in the Russian Federation over 14 years (2006–2019) using mathematical models (linear, logarithmic, power, and exponential approximation).An optimal mathematical model was selected using three statistical parameters, namely determination coefficient, Fischer’s exact test, and standard error. Periodicity of rises and falls in morbidity was calculated with Fourier one- dimensional spectral analysis. Intra-year dynamics of morbidity with EVnI was estimated basing on monthly spread of the disease cases on the RF territory. Classic seasonal decomposition, Census I technique, was applied to analyze time series of monthly morbidity. It was determined that EVnI epidemic process was unevenly spread over years in the RF in the examined period of time (2006–2019) and there were two opposite trends in it; the first one lasted from 2006 to 2010 when morbidity was declining and the second was from 2010 to 2019 when it was growing. Having analyzed manifestations of EVnI epidemi- ologic process in long-term dynamics given its uneven spread as per years, we established that it was advisable to use mathematical models approximated as per separate time periods. Average long-term morbidity with EVnI amounted to 8.09 0/0000 in the RF in 2010–2019 with growth rate being equal to 17.7 %. Maximum value was registered in 2017 (16.32 0/0000). An unfavorable prediction for further epidemic situation development was revealed for the examined pe- riod. The epidemic process was characterized with 4-year periodicity and summer-autumn seasonality with peaks usually occurring in August and September. Rates that characterized intensity of the trends in long-term morbidity dynamics and were calculated with mathematical models differed authentically from those obtained via conventional calculations of average values (χ=11.08; d.f.=1; p=0.0009).

Introduction . SARS-CoV-2 can be transmitted by infected people without or with mild symptoms of acute respira-tory infection (ARI). Monitoring based on nucleic acid amplification techniques is used to measure the prevalence of ARI pathogens and to assess the effectiveness of preventive measures. The aim is to measure the prevalence of pathogens causing ARIs of viral etiology, influenza, and COVID-19 among individuals without ARI symptoms throughout age groups, to trace changes in the epidemic situation by weekly monitoring pathogens during the inter-epidemic period and at the beginning of a typical ARI epidemic season, to assess the effectiveness of medical masks for prevention of the above infections. Materials and methods . A total of 14,119 people (including 4,582 children) without ARI symptoms went through examination, including questionnaire surveys, in 26 regions of Russia from August to October 2020. Nasopharyn-geal and oropharyngeal swabs were tested by using AmpliSens ARVI-screen-FL, AmpliSens Influenza virus A/B-FL, and AmpliSens Cov-Bat-FL reagent kits (The Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow). Results. 11.1% of the tested samples showed positive results; the rhinovirus prevailed (7.32%), while SARS-CoV-2 was detected in 1.66%. In autumn, the proportion of SARS-CoV-2 infected cases increased from 0.49% to 4.02% (p < 0.001). The SARS-CoV-2 RNA concentration was up to 1010 copies/mL. Conclusions. Differences in the prevalence of SARS-CoV-2 and rhinovirus among the age groups and over time were found and analyzed. Using of medical masks reduced the risk of infection with respiratory viruses and with SARS-CoV-2 by 51% and 34%, respectively. In case of prolonged exposure to a COVID-19 patient, healthy people must use a respirator for more effective protection. The individuals whose work was associated with a high level of social contacts were infected more rarely than other individuals in the same age group (p = 0.001); this fact supports the importance of anti-epidemic measures and commitment to their adherence by people whose profession entails frequent social contacts.

Advances in the diagnosis and treatment of patients with infectious endocarditis are limited by the high frequency of cases with an unknown etiology and imperfection of microbiological (cultural) methods. To overcome these problems new approaches to the identification of infectious endocarditis pathogens were introduced, which allowed achieving certain positive results. However, it should be noted that despite the wide variety of diagnostic tools currently used, there is no ideal method for etiological laboratory diagnosis of infectious endocarditis. The article discusses the features and place of immunochemical, molecular biological (MALDI-TOF MS, real-time PCR, sequencing, in situ fluorescence hybridization, metagenomic methods, etc.), immunohistochemical methods, and their advantages and limitations.

Introduction. Currently, the number of confirmed cases of COVID-19 among healthcare workers continues to increase both in Russia and in other countries. Due to their professional activities' specifics, medical workers - frequent contact with sick people are most at risk of contracting SARS-CoV-2. The study aims to research the risk factors for infection of medical workers with SARS-CoV-2 to prevent infection and the spread of COVID-19 in medical institutions, considering the use of personal protective equipment. Materials and methods. Specialists of the Central Research Institute of Epidemiology of Rospotrebnadzor conducted an anonymous questionnaire with the subsequent analysis of the results obtained to study and assess risk factors for infection of SARS-CoV-2 medical workers, their attitude to the use of personal protective equipment, non-specific prophylaxis. Results. The authors present a literature review on the problem of infection and morbidity of COVID-19 medical workers, who are known to be at high risk of infection due to frequent contact with the sick. We analyzed data that exposure to higher concentrations of the virus, especially from critically ill patients, can affect the disease's severity in health care workers. The authors conducted an anonymous survey to study the risk factors for infection of health care workers with SARS-CoV-2 and their attitude to the use of personal protective equipment. Based on the obtained data, identified the main ways of infection of medical staff, options of the disease, and their severity, and revealed that providers responsible for selecting and using PPE. Conclusion. Assessing potential risk factors for the spread of coronavirus infection among healthcare workers is essential to prevent healthcare workers' infection and the spread of COVID-19 in healthcare settings.

Objective. To analyze the efficacy of antiviral therapy for chronic hepatitis C (HCV) in children. Patients and methods. This study included 58 children aged between 3 and 17 years who had never received antiviral therapy (AVT) before and were treated in the Pediatric Department for Infectious Diseases, N.A.Semashko City Clinical Hospital No 2 (Samara). The inclusion criteria were as follows: confirmed CHC diagnosis and follow-up for at least one year. We analyzed treatment outcomes during an 8-year period, as well as the dynamics of clinical and biochemical parameters in children with HCV depending on their response to AVT. Results. Sustained virologic response (SVR) was achieved in 19 out of 58 children (32.8%) after 24 weeks of therapy and 30 out of 58 children (51.7%) after 48 weeks of therapy. In these children, viral genotypes were distributed as follows: 1b genotype in 19 participants (32.7%), 2a genotype in 4 participants (6.9%), and 3a genotype in 7 participants (12.1%). Twenty-eight patients (71.8%) remained HCV RNA positive, including 1 child with 2a genotype (2.6%), 3 children with 3a genotype (7.7%), and 24 children with 1b genotype (61.5%). Three years after treatment completion, 25 out of 58 patients (43.1%) had SVR. During 8 years of follow-up, 17 out of 30 children (56.7%) maintained SVR. Conclusion. Five out of 58 study participants (8.6%) developed F1–F2 liber fibrosis (METAVIR scale) over 8 years of follow-up. Two out of 58 children with HCV (3,5%) were found to have liver cirrhosis 6.6 ± 1.15 years after the disease onset (minimum – 4 years; maximum – 8 years). New drugs and treatment regimens are needed to increase the SVR rate in children. Key words: children, outcomes, sustained virologic response, chronic hepatitis C

Objective of the research: to determine clinical and epidemiological features of the course of the new coronavirus infection (COVID-19) caused by SARS-CoV-2 in children in the Russian Federation (RF) Materials and methods: a retrospective analysis of all confirmed COVID-19 cases in children in the first half of 2020 in the Russian Federation was performed Information about patients (age, sex, examination date, place of residence, disease severity final diagnosis, etc ) was taken from the database containing the Rospotrebnadzor report form № 970 «Information on cases of infectious diseases in persons with suspected new coronavirus infection» January - June 2020 across the Russian Federation Research results were processed using the IBM SPSS Statistics 26 program To assess the differences in nominal indicators (proportions), the Pearson x2 test was used The results were considered statistically significant at p0,05) In children, the maximum number of cases is registered in family foci - 75% Upper respiratory tract infections were diagnosed in 72,1% of patients The proportion of pneumonia was 1,8%, and ⅔ of children were over 3 years old (p0 C Cough was registered in 50,8% of cases Rhinitis/rhinopharyngitis developed only in every 4th child Symptoms pathognomonic for COVID-19, such as loss of smell (anosmia) and taste (ageusia), were recorded only in 17% of cases 41,3% of patients received treatment in a hospital, and among them children under 3 years of age predominated Conclusion: in children in the RF, the new coronavirus infection COVID-19 is generally favorable Цель исследования: определить клинико-эпидемиологические особенности течения новой коронавирусной инфекции (COVID-19), вызванной SARS-CoV-2, у детей в Российской Федерации (РФ) Материалы и методы исследования: проведен ретроспективный анализ всех случаев подтвержденной COVID-19 у детей в первом полугодии 2020 г в РФ Информация о пациентах (возраст, пол, дата обследования, место жительства, тяжесть болезни, заключительный диагноз и др ) взята из базы данных, содержащей формы отчета Роспотребнадзора № 970 «Информация о случаях инфекционных заболеваний у лиц с подозрением на новую коронавирусную инфекцию» за январь-июнь 2020 г по РФ Результаты исследования обработаны с использованием программы IBM SPSS Statistics 26 Для оценки различий номинальных показателей (долей) использовали критерий х2 Пирсона Результаты считали статистически значимыми при р0,05) У детей максимальное количество случаев болезни регистрируется в семейных очагах - 75% Инфекции верхних дыхательных путей были диагностированы у 72,1% пациентов Доля пневмоний составила 1,8%, при этом ⅔ детей были старше 3 лет (р0 С была выявлена лишь у 3,5% детей Кашель регистрировался в 50,8% случаев Ринит/ринофарингит развивался лишь у каждого 4-го ребенка Такие патогномоничные для COVID-19 симптомы, как потеря обоняния (аносмия) и вкуса (агевзия), регистрировались только в 17% случаев 41,3% пациентов получали лечение в стационаре, при этом среди госпитализированных преобладали дети до 3 лет Заключение: у детей новая коронавирусная инфекция COVID-19 в РФ протекает в целом благоприятно

The HIV cascade model can be used as an epidemiological surveillance tool and for assessing the quality of medical care for HIV-positive people. It is possible to use the model for the entire population of people living with HIV, in various socio-demographic groups, by region, years and other indicators. This article describes the features of a HIV cascade model depending on the goals for its use.Каскадная модель медицинской помощи людям, живущим с ВИЧ, может быть использована в качестве инструмента эпидемиологического надзора и как один из компонентов оценки медицинской помощи ВИЧ-позитивным лицам. При необходимости и наличии данных возможно применение модели для всей популяции людей, живущих с ВИЧ, в различных социально-демографических группах или при оказании специальных видов помощи, по регионам, годам и другим показателям. В статье описаны особенности построения каскадной модели в зависимости от поставленных целей ее использования.

The article presents an analysis of the primary incidence of hepatitis B in the Samara region from 1997 to 2018. It was noted that during the 1997–2000 period there was an increase in the carrying levels of viral hepatitis B agent, the incidence of acute hepatitis B, first detected by chronic hepatitis B. Since 2000–2001, there has been a dynamic decrease in the incidence of hepatitis B. It should be noted that from the 2006 (beginning of immunoprophylaxis) to 2018. in the Samara region more intensive decrease in indicators of incidence of hepatitis B was noted. Rates of decrease in incidence of an acute hepatitis In from 2006 to 2018 in the Samara region from 7,10 ⁄ 0000 to 0,70 ⁄ 0000v 10,1 times were observed (p < 0.01). Decrease in incidence of chronic hepatitis B was noted from 2006 to 2018 by 1.4 times (p < 0.01) from 14,50 ⁄ 0000 to 10,30 ⁄ 0000. Decrease in indicators of carriage of the causative agent of viral hepatitis B from 2006 to 2018 happened more in high gear, in comparison with indicators of incidence of chronic hepatitis B to 55,60 ⁄ 0000 to 6,60 ⁄ 0000 by 8.4 times (p < 0.01). From 2008 to 2018, the vaccination coverage against hepatitis B of the child population was 99.3–99.5 %, which led to a significant decrease in the incidence of hepatitis B in the Samara region. From 2011 to 2018, no cases of acute hepatitis B of the child population of the Samara region were registered. In the last three years, no cases of chronic hepatitis B of the child population have been recorded in the Samara region.

An epidemic of COVID-19 (Coronavirus disease 2019) etiologically associated with the SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus 2) that occurred at the turn of 2019–2020 firstly in Wuhan (Hubei province of China) and then spread to many countries around the world rose a new wave of interest to coronaviruses. The first coronaviruses – members of the Coronaviridae family belonging to the order Nidovirales — were discovered in the first half of the last century. The first human coronavirus, HCoV-B814, was isolated in 1965 that was not preserved in available virological collections. Over the last time, old-fashioned names and terms have been overlapped. By the beginning of the XXI century coronaviruses posed a serious veterinary problem but it was believed that epidemic coronaviruses were not among highly dangerous viruses. Scientific community had to revise such views first in 2002 when SARS-CoV (Severe acute respiratory syndrome-related coronavirus) was transferred to human population in the Southeast Asia from bats, and then in 2012 when natural foci of the MERS-CoV (Middle East respiratory syndrome-related coronavirus) were found on the territory of the Arabian Peninsula. Due to an increased interest in coronaviruses, a large number of new Coronaviridae members was discovered in the first two decades of the XXI century, which required to revise its taxonomic structure several times. This review is aimed at outlining a history of investigating coronaviruses and their current classification that was shaped in early 2020 in accordance to the last recommendations of the International Committee on Taxonomy of Viruses.

Pseudomonas aeruginosa is a member of the ESKAPE opportunistic pathogen group, which includes six species of the most dangerous microbes. This pathogen is characterized by the rapid acquisition of antimicrobial resistance, thus causing major healthcare concerns. This study presents a comprehensive analysis of clinical P. aeruginosa isolates based on whole-genome sequencing data. The isolate collection studied was characterized by a variety of clonal lineages with a domination of high-risk epidemic clones and different CRISPR/Cas element patterns. This is the first report on the coexistence of two and even three different types of CRISPR/Cas systems simultaneously in Russian clinical strains of P. aeruginosa. The data include molecular typing and genotypic antibiotic resistance determination, as well as the phylogenetic analysis of the full-length cas gene and anti-CRISPR genes sequences, predicted prophage sequences, and conducted a detailed CRISPR array analysis. The differences between the isolates carrying different types and quantities of CRISPR/Cas systems were investigated. The pattern of virulence factors in P. aeruginosa isolates lacking putative CRISPR/Cas systems significantly differed from that of samples with single or multiple putative CRISPR/Cas systems. We found significant correlations between the numbers of prophage sequences, antibiotic resistance genes, and virulence genes in P. aeruginosa isolates with different patterns of CRISPR/Cas-elements. We believe that the data presented will contribute to further investigations in the field of bacterial pathoadaptability, including antimicrobial resistance and the role of CRISPR/Cas systems in the plasticity of the P. aeruginosa genome.

The main direction of improving the quality of medical care for pregnant women, mothers and newborns is to improve the diagnosis and prevention of inflammatory infections, including healthcare-associated infections (HAI). A huge number of types of causative agents of opportunistic infections in women and newborns significantly complicates the etiological diagnosis and timely, adequate treatment at all stages of medical care. Recently, we have seen the emergence and spread of multi-resistant strains: bacteria from the ESKAPE-pathogens group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeroginosa, Enterobacter cloacae); as well as coagulase-negative staphylococci and yeasts, which easily realize their pathogenic potential for immunocompromised patients. The changed epidemiological situation requires the creation and functioning of a local system of surveillance of opportunistic infections in obstetrics and neonatology, primarily for the HAI, which will quickly monitor changes occurring in the etiological, intraspecific, strain structure of pathogens and respond to them in a timely manner. The evolution of technologies in microbiology allows introducing new approaches to the diagnosis, prevention and treatment of infections. Active use of modern methods of etiological diagnostics, development and application of innovative antimicrobial drugs in combination with coordinated work of physicians, microbiologists, clinical pharmacologists, epidemiologists and specialists in the field of molecular biology and bioinformatics is the key to the formation of new opportunities for epidemiological surveillance and prevention of infections in childbirth.

Background: chronic hepatitis is a common infection in all age groups. The optimization of therapeutic approaches is an important medical social and national economic issue. Aim: to describe the clinical and laboratory features of chronic hepatitis B (CHB) in children depending on the efficacy of antiviral therapy. Patients and Methods: 31 children aged 3–17 years with НBeAg-negative CHB who were treated in the Children’s Infectious Department of N.A. Semashko Samara City Clinical Hospital No. 2 and then monitored in a children’s hepatological center were enrolled. These children received no prior antiviral treatment. T he efficacy of antivirals and CHB outcomes over a 6-year perio d were evaluated. Results: the changes in clinical and biochemical parameters in children with CHB depending on treatment response were analyzed. All children were prescribed with antiviral therapy according to Diagnosis and Treatment Protocol for Hepatitis B and C (2010). In 14 (45.2%) children who received antiviral therapy, sustained virologic response was achieved after 48 weeks. In these children, no cases of liver fibrosis were reported over a 6-year period. Meanwhile, in the group without sustained virologic response after antiviral therapy (n=17), 1 patient was diagnosed with liver fibrosis stage 1 and 2 patients were diagnosed with Child class A cirrhosis. Conclusion: despite countrywide HBV vaccination, the incidence of CHB is still high thus requiring the development of novel diagnostic and therapeutic strategies. KEYWORDS: chronic hepatitis B, children, differential therapy, viral host response, prognosis. FOR CITATION: Churbakovа O.V., Akimkin V.G., Pechkurov D.V. Clinical features of chronic B hepatitis in children depending on treatment response. Russian Medical Inquiry. 2020;4(11):682–686. DOI: 10.32364/2587-6821-2020-4-11-682-686.

Background The dual infection with SARS-CoV-2 is poorly described and is currently under discussion. We present a study of two strains of SARS-CoV-2 detected in the same patient during the same disease presentation. Case presentation A patient in their 90 s was hospitalised with fever. Oropharyngeal swab obtained on the next day (sample 1) tested positive for SARS-CoV-2. Five days later, the patient was transferred to the ICU (intensive care unit) of the hospital specialising in the treatment of COVID-19 patients, where the patient's condition progressively worsened and continuous oxygen insufflation was required. Repeated oropharyngeal swab (sample 2), which was taken eight days after the first one, also tested positive for SARS-CoV-2. After 5 days of ICU treatment, the patient died. The cause of death was a coronavirus infection, which progressed unfavourably due to premorbid status. We have performed sequencing of full SARS-CoV-2 genomes from oropharyngeal swabs obtained eight days apart. Genomic analysis revealed the presence of two genetically distant SARS-CoV-2 strains in both swabs. Detected strains belong to different phylogenetic clades (GH and GR) and differ in seven nucleotide positions. The relative abundance of strains was 70% (GH) and 30% (GR) in the first swab, and 3% (GH) and 97% (GR) in the second swab. Conclusions Our findings suggest that the patient was infected by two genetically distinct SARS-CoV-2 strains at the same time. One of the possible explanations is that the second infection was hospital-acquired. Change of the dominant strain ratio during disease manifestation could be explained by the advantage or higher virulence of the GR clade strain.

Acinetobacter baumannii is a dangerous bacterial pathogen possessing the ability to persist on various surfaces, especially in clinical settings, and to rapidly acquire the resistance to a broad spectrum of antibiotics. Thus, the epidemiological surveillance of A. baumannii within a particular hospital, region, and across the world is an important healthcare task that currently usually includes performing whole-genome sequencing (WGS) of representative isolates. During the past years, the dissemination of A. baumannii across the world was mainly driven by the strains belonging to two major groups called the global clones or international clones (ICs) of high risk (IC1 and IC2). However, currently nine ICs are already considered. Although some clones were previously thought to spread in particular regions of the world, in recent years this is usually not the case. In this study, we determined five ICs, as well as three isolates not belonging to the major ICs, in one multidisciplinary medical center within the period 2017–2019. We performed WGS using both short- and long-read sequencing technologies of nine representative clinical A. baumannii isolates, which allowed us to determine the antibiotic resistance and virulence genomic determinants, reveal the CRISPR/Cas systems, and obtain the plasmid structures. The phenotypic and genotypic antibiotic resistance profiles are compared, and the possible ways of isolate and resistance spreading are discussed. We believe that the data obtained will provide a better understanding of the spreading and resistance acquisition of the ICs of A. baumannii and further stress the necessity for continuous genomic epidemiology surveillance of this problem-causing bacterial species.

Since the outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 coronavirus, the international community has been concerned about the emergence of mutations that alter the biological properties of the pathogen, for example, increasing its infectivity or virulence. In particular, since the end of 2020, several variants of concern have been identified around the world, including variants “alpha” (B.1.1.7, “British”), “beta” (B.1.351, “South African”), “gamma” (P.1, “Brazilian”) and “delta” (B.1.617.2, “Indian”). However, the existing mechanism for searching for important mutations and identifying strains may not be effective enough, since only a relatively small fraction of all identified pathogen samples can be examined for genetic changes by whole genome sequencing due to its high cost. In this study, we used the method of targeted high-throughput sequencing of the most significant regions of the gene encoding the S-glycoprotein of the SARS-CoV-2 virus, for which a primer panel was developed. Using this technique, we examined 579 random samples obtained from patients in Moscow and the Moscow region with coronavirus infection from February to June 2021. The study demonstrated the dynamics of the representation in the Moscow region of a number of SARS-CoV-2 strains and its most significant individual mutations in the period from February to June 2021. It was found that the strain B.1.617.2 began to spread rapidly in Moscow and the Moscow region in May, and in June it became dominant, partially displacing other varieties of the virus. The results obtained make it possible to accurately determine the belonging of the samples to the abovementioned and some other strains. The approach can be used to standardize the procedure for searching for new and existing epidemiologically significant mutations in certain regions of the SARS-CoV-2 genome, which allows studying a large number of samples in a short time and to get a more detailed picture of the epidemiological situation in the region.

Monitoring online queries can provide early and accurate information about the spread of COVID-19 in the population and about the effectiveness of COVID-19 epidemic control measures.The purpose of the studyAssessment of significance of online queries regarding smell impairment to evaluate the epidemiological status and effectiveness of COVID-19 epidemic control measures.Materials and methodsWeekly online queries from Yandex Russian users regarding smell impairment were analysed in regions and large cities of Russia from 16/3/2020 to 21/2/2021. A total of 81 regions of Russia and several large cities, such as Moscow, St. Petersburg, and Nizhny Novgorod, were included in the study.ResultsA strong positive direct correlation (r>0.7) was found between the number of smell-related queries in Yandex new cases of COVID-19 in 59 out of 85 Russian regions and large cities (70%). During the “first” peak of COVID-19 incidence in Russia (April-May 2020), the increase in the number of smell-related queries outpaced the increase in the number of new cases by 1-2 weeks in 23 out of 59 regions of Russia. During the “second” peak of COVID-19 incidence in Russia (October-December 2020), the increase in the number of smell-related queries outpaced the increase in the number of new cases by 1-2 weeks in 36 regions of Russia, including Moscow. We also estimated the increase in the query/new case ratio during the “second” peak of incidence for 45 regions. It was found that the query/new case ratio increased by more than 100% in 24 regions. The regions where the increase in queries was more than 160% compared to new infection cases during the “second” peak of incidence demonstrated significantly higher search activity related to levofloxacin than the regions where the increase in queries was lower than 160% compared to the increase in new infection cases.ConclusionThe sudden interest in smell impairment and growing frequency of online queries among the population can be used as an indicator of the spread of coronavirus infection among the population as well as for evaluation of the effectiveness of COVID-19 epidemic control measures.

This review presents the basic principles of application of the loop-mediated isothermal amplification (LAMP) reaction for the rapid diagnosis of coronavirus infection caused by SARS-CoV-2. The basic technical details of the method, and the most popular approaches of specific and non-specific detection of amplification products are briefly described. We also discuss the first published works on the use of the method for the detection of the nucleic acid of the SARS-CoV-2 virus, including those being developed in the Russian Federation. For commercially available and published LAMP-based assays, the main analytical characteristics of the tests are listed, which are often comparable to those based on the method of reverse transcription polymerase chain reaction (RT-PCR), and in some cases are even superior. The advantages and limitations of this promising methodology in comparison to other methods of molecular diagnostics, primarily RT-PCR, are discussed, as well as the prospects for the development of technology for the detection of other infectious agents.

Acinetobacter baumannii is an opportunistic pathogen being one of the most important causative agents of a wide range of nosocomial infections associated with multidrug resistance and high mortality rate. This study presents a multiparametric and correlation analyses of clinical multidrug-resistant A. baumannii isolates using short- and long-read whole-genome sequencing, which allowed us to reveal specific characteristics of the isolates with different CRISPR/Cas systems. We also compared antibiotic resistance and virulence gene acquisition for the groups of the isolates having functional CRISPR/Cas systems, just CRISPR arrays without cas genes, and without detectable CRISPR spacers. The data include three schemes of molecular typing, phenotypic and genotypic antibiotic resistance determination, as well as phylogenetic analysis of full-length cas gene sequences, predicted prophage sequences and CRISPR array type determination. For the first time the differences between the isolates carrying Type I-F1 and Type I-F2 CRISPR/Cas systems were investigated. A. baumannii isolates with Type I-F1 system were shown to have smaller number of reliably detected CRISPR arrays, and thus they could more easily adapt to environmental conditions through acquisition of antibiotic resistance genes, while Type I-F2 A. baumannii might have stronger “immunity” and use CRISPR/Cas system to block the dissemination of these genes. In addition, virulence factors abaI, abaR, bap and bauA were overrepresented in A. baumannii isolates lacking CRISPR/Cas system. This indicates the role of CRISPR/Cas in fighting against phage infections and preventing horizontal gene transfer. We believe that the data presented will contribute to further investigations in the field of antimicrobial resistance and CRISPR/Cas studies.

Despite the accumulated global experience in the fight against the COVID-19 pandemic, the issues of diagnosis, treatment and prognosis of the disease are still insufficiently studied. According to a number of publications, vascular dysfunction caused by the SARS-CoV-2 virus is one of the leading links in pathogenesis. Timely correction of vascular disorders can significantly reduce the number of adverse outcomes. The article presents the results of a study of changes in the value of markers that characterize the state of the cardiovascular system in patients with COVID-19.The aim of the study was to objectively assess the severity of cardiovascular damage in patients with CAVID-19 in the early stages and during the period of convalescence. Materials and Methods: The study included 205 people aged 18 to 85 years. A new coronavirus infection caused by the SARS-CoV-2 virus was confirmed in 190 patients, and 15 people were in contact with COVID-19 patients. The significance of markers of cardiovascular disease in COVID-19 was assessed in 15 patients (the main group) who had clinical symptoms of the acute phase of coronavirus infection and the duration of symptoms was no more than 6 days. The comparison group 1 included 32 patients at a period of 28±1 day from the moment of the appearance of the first symptoms of coronavirus infection, who, after the course of treatment, recovered. The significance of the indicators was clarified by comparing the obtained values with the comparison group 2, which included persons who had contact with COVID-19 patients. The main group and the comparison groups were comparable in age, gender composition, and comorbidity. The study evaluated the values of endothelin-1 in the blood serum of patients of the compared groups. Additionally, MB-creatine kinase, troponin I, and brain natriuretic peptide were determined in blood samples in patients with COVID-19. Results: According to the results of the assessment of the average values, the level of endothelin-1 in the groups with acute manifestations of COVID-19 and among those who came into contact with patients was significantly higher than in patients after achieving a good result of therapy, p = 0.004. There were no significant differences in the assessment of the level of other markers. An increase in the marker of vascular damage endothelin-1 in asymptomatic individuals who have come into contact with patients with coronavirus infection can be used for early detection of vascular pathology. Conclusions: The determination of endothelin-1 levels in COVID-19 patients at various stages of the disease can be used as a sensitive marker of vascular damage for early determination of the prognosis of the course of the disease and its outcomes. Funding Statement: No pharmaceutical companies participated in the preparation and creation of this publication. State budget financing on behalf of the Government of the Russian Federation and the Federal Service for Supervision of Consumer Rights Protection and Human Welfare for 2020 in the direction of the Industry Research Program of Rospotrebnadzor and the subject of the State Task for 2016-2020. Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: The study was approved by the local ethics committee.

An analysis of published literature data on the relationship of parasitic diseases and oncogenesis is carried out. Current knowledge about the association of parasitic infections and cancer formation has revealed several carcinogenic mechanisms, but the severity of the relationship between parasites and cancer formation (except for schistosome, opisthorchis and clonorchis) should be confirmed in future experimental and population studies.Проведен анализ опубликованных данных о взаимосвязи паразитарных заболеваний и онкопатологий. Современные знания об ассоциации паразитарных инфекций и онкогенеза выявили несколько канцерогенных механизмов, но выраженность связи между паразитами и формированием рака (кроме шистосомы, описторхиса и клонорхиса) должна быть подтверждена в будущих экспериментальных и популяционных исследованиях.

SummaryBackgroundThe effect of SARS-CoV-2 mutations and viral load on the severity of COVID-19 is not well understood. The possibility of reinfection with SARS-CoV-2 has already been reported, but dual infection with SARS-CoV-2 is poorly described and is currently under discussion. We describe a study of two strains of SARS-CoV-2 detected in the same patient during the same disease presentation.MethodsTwo nasopharyngeal swabs were obtained eight days apart from the patient in their 90s, diagnosed with lobar pneumonia (J18.1). Both tests were positive for SARS-CoV-2 with high viral load (Ct = 13). We have performed high-throughput sequencing of SARS-CoV-2 genomes from both swabs.FindingsGenomic analysis of SARS-CoV-2 revealed the presence of two genetically distant strains in both swabs. Detected strains belong to different phylogenetic clades (GH and GR) and differ in the seven nucleotide positions. The relative abundance of strains was 70% (GH) and 30% (GR) in the first swab, and 3% (GH) and 97% (GR).InterpretationOur findings suggest that the patient was infected by two genetically distinct SARS-CoV-2 strains at the same time. One of the possible explanations is that the second infection occurred in the hospital. Change of the dominant strain ratio during disease manifestation could be explained by the advantage or higher virulence of the strain belonging to the clade GR.

The increasing trend in antimicrobial resistance of pathogenic bacteria dictates the need for alternative solutions. Bacteriophages are bacterial viruses that kill their hosts during the lifecycle. The high specificity of phages makes the production of personalized cocktails the best option. Registration of drugs with variable composition lies beyond the current legal policies. In the present review, we studied the regulatory framework of the top 10 world economies from the point of personalized bacteriophages registration. We underlined procedures that countries can learn from each other.

Introduction. The novel SARS-CoV-2 coronavirus, which emerged at the end of 2019 and caused a worldwide pandemic, triggered numerous questions about the epidemiology of the novel COVID-19 disease and about wellknown coronavirus infections, which used to be given little attention due to their mild symptoms. The purpose : The routine screening-based multiyear retrospective observational study of prevalence and circulation patterns of epidemic-prone human coronaviruses in Moscow. Material and methods . The real-time polymerase chain reaction was used to detect RNA of human coronaviruses (HCoVs) in nasal and throat swabs from 16,511 patients with an acute respiratory infection (ARI), aged 1 month to 95 years (children accounted for 58.3%) from January 2016 to March 2020, and swabs from 505 relatively healthy children in 2008, 2010 and 2011. Results. HCoVs were yearly found in 2.6–6.1% of the examined patients; the detection frequency was statistically higher in adults than in children, regardless of sex. At the height of the disease incidence in December 2019, HCoVs were detected in 13.7% of the examined, demonstrating a two-fold increase as compared to the multi-year average for that month. The statistical frequency of HCoV detection in ARI pediatric patients under 6 years was significantly higher than in their healthy peers (3.7 vs 0.7%, p = 0.008). Conclusion . HCoVs circulate annually, demonstrating a winter-spring seasonal activity pattern in the Moscow Region and reaching peak levels in December. Over the years of observation, the HCoV epidemic activity reached maximum levels in December 2019–February 2020 and decreased in March to the multi-year average. Amid a growing number of SARS-CoV-2 cases imported to Moscow in March 2020, the HCoV detection frequency dropped sharply, which can be explained by the competition between different coronaviruses and by the specificity of HCoV detection with the diagnostic test kit used in this study.

Mycoplasma genitalium is a widespread sexually transmitted infection (STI) with growing rate of antimicrobials resistance. In our study, 137 vaginal and 131 urethral M. genitalium–positive swabs were sequentially collected through the work of Reference Center for STI during 2019. For prevalence evaluation of macrolide-resistance mutations three commercially available kits were used: AmpliSens® M. genitalium-ML/FQ-Resist-FL (Central Research Institute of Epidemiology, Russia), ResistancePlus® MG (SpeeDx, Australia), and S-DiaMGRes™ (Diagenode, Belgium). Macrolide resistance mutations were detected in 16% (43 of 268) of samples. Diagnostic characteristics were evaluated against Sanger sequencing. For AmpliSens® M. genitalium-ML/FQ-Resist-FL specificity was shown to be 100% (CI 95%, 98.4–100), and sensitivity was 90.7% (CI 95%, 77.9–97.4). ResistancePlus® MG specificity was 100% (CI 95%, 98.3–100), and sensitivity was 92.1% (CI 95%, 78.6–98.3). S-DiaMGRes™ specificity was shown to be 88.6% (CI 95%, 83.9–92.4), and sensitivity was 100% (CI 95%, 84.4–100). Mutations of parC gene region were detected in 14.5% (38 of 268) using AmpliSens® M. genitalium-ML/FQ-Resist-FL with further validation by Sanger sequencing. Of studied samples, 6.3% (17 of 268) contained both antimicrobials of class resistance mutations. Prevalence of macrolide-resistant M. genitalium in Moscow was 21.7% (23 of 106) and of fluoroquinolone-resistant M. genitaliuim was 20.8% (22 of 106). In Moscow region, macrolide-resistant M. genitalium were 12.3% (20 of 162) and 9.9% (16 of 162) of fluoroquinolone-resistant M. genitalium. All three kits can be used both for epidemiological monitoring of M. genitalium presence and mutation prevalence estimation. In Moscow, macrolide- and fluoroquinolone-resistant mutant prevalence increased in 3.9 and 2.7 times in 3 years.

Klebsiella pneumoniae is one of the most important pathogens concerned with multidrug resistance in healthcare-associated infections. The treating of infections caused by this bacterium is complicated due to the emergence and rapid spreading of carbapenem-resistant strains, which are associated with high mortality rates. Recently, several hypervirulent and carbapenemase-producing isolates were reported that make the situation even more complicated. In order to better understand the resistance and virulence mechanisms, and, in turn, to develop effective treatment strategies for the infections caused by multidrug-resistant K. pneumoniae, more comprehensive genomic and phenotypic data are required. Here, we present the first detailed molecular epidemiology report based on second and third generation (long-read) sequencing for the clinical isolates of K. pneumoniae in the Russian Federation. The data include three schemes of molecular typing, phenotypic and genotypic antibiotic resistance determination, as well as the virulence and plasmid profiling for 36 K. pneumoniae isolates. We have revealed 2 new multilocus sequence typing (MLST)-based sequence types, 32 multidrug-resistant (MDR) isolates and 5 colistin-resistant isolates in our samples. Three MDR isolates belonged to a very rare ST377 type. The whole genome sequences and additional data obtained will greatly facilitate further investigations in the field of antimicrobial resistance studies.

The high prevalence of the hepatitis B virus (HBV) in population occurs mainly due to numerous mechanisms formed in the process of the virus evolution, contributing to its survival under immunological pressure. The review presents the most complete systematization and classification of various HBV protective mechanisms basing on their influence on different parts of congenital and adaptive immune response. The analysis of literature data allows for the conclusion that two basic principles underlie the mechanisms: the strategy of the «stealth virus» (virus’s escape from recognition by the immune system) and strategy of immunosuppression. The stealth virus strategy is performed as follows: special strategy of the HBV replication which prevents the recognition by the receptors of congenital immune system; occurrence of the vaccine escape mutants; isolation of the virus in host cells and tissues providing its inaccessibility to T-cells along with hyperproduction of subviral particles as traps for specific antibodies. The core principle of the immunosuppression implemented in hepatitis B therapy is based on the phenomenon of the viral apoptotic mimicry. The result of this interaction strategy is dysfunction of NK and NKT-cells, inactivation of dendritic cell functions, and suppression of the adaptive immune response. The review demonstrates that interaction between HBV and the immune system of the macro organism is in some kind of «dynamic equilibrium» depending on numerous factors. Specific molecular targets of the viral impact are described. We propose to expand the research on the influence of the host’s genetic factors on the development of congenital and adaptive immune response against HBV, especially during the real infectious process which results in the improvement of approaches to the therapy by developing personalized treatment methods.

Provision of infection security in transplantology and transfusiology is a challenging and significant problem that depends on the quality of medical donor selection and laboratory diagnosis of the blood collected. At present, a large number of blood-borne viruses are known; nevertheless, in Russia, the list of viral agents to be tested during the examination by the blood service boils down to three ones: HIV, hepatitis C and hepatitis B viruses.The review article demonstrates the need for implementation of additional laboratory tests for the agents of the priority healthcare-associated blood-borne infections (HAI) using a risk-based approach, i.e., on specified sites and in high risk groups. It presents a methodology for determination of a quantitative blood-induced infection residual risk (BIRR) index to be used while evaluating the efficiency of viral security provision in the blood service.

In 2018, a previously unknown Ebola virus, Bombali virus, was discovered in Sierra Leone. We describe detection of Bombali virus in Guinea. We found viral RNA in internal organs of 3 Angolan free-tailed bats (Mops condylurus) trapped in the city of N’Zerekore and in a nearby village.

Immunological efficacy of mass vaccine prevention of hepatitis B was studied in the framework of the National Priority Project "Health" in some regions of the Russian Federation. Markers of hepatitis B (HbsAg, anti-HBs with the determination of their concentration, anti-HBcor summary and class IgM) were determined with the use of commercial test systems by chemiluminescence enzyme immunoassay analyzer the "Architect" of the company «Abbott» (USA) at different times after the completion of vaccination