Факторы, влияющие на тяжесть течения COVID-19 и развитие осложнений

Due to the prevalence and diversity of both symptoms and outcomes of COVID-19, the understanding of the factors that determine the risk of severe course of this disease and possible complications is of particular importance. In this review, we present the information on specifics of COVID-19 pathogenesis and give a theoretical justification for the factors that determine the course of this disease in patients of different age groups, patients with chronic pathology, and pregnant women. Particular attention is paid to the post-COVID syndrome.В связи с широким распространением и «многоликостью» как симптоматики, так и исходов COVID-19 особую актуальность приобретает понимание факторов, определяющих риск тяжелого течения заболевания и возможных осложнений. В обзоре представлена информация об особенностях патогенеза COVID-19, дали теоретическое обоснование факторов, обусловливающих особенности заболевания у пациентов разных возрастных групп, беременных, а также при хронических патологиях. Отдельное внимание уделено постковидному синдрому

Фено- и генотипический портрет штаммов Yersinia pestis филогрупп 2.MED4 и 2.MED1 – этиологических агентов вспышек чумы ХХ века в Прикаспийском регионе

We performed a comparative analysis of the phenotypic and genotypic characteristics of strains of the plague pathogen of phylogroups 2.MED4 and 2.MED1 of the medieval biovar of the main subspecies from epidemically active plague foci in the Caspian Sea region in the XX century. According to the results of the analysis, biochemical properties, nutritional requirements and plasmid profile of strains of phylogroups 2.MED4 and 2.MED1 of the medieval biovar of Y. pestis were determined. Genetic variability in the hemS, caf1M, and ssaJ genes associated with the virulence in strains of the 2.MED lineage was revealed. The data obtained on the phenotypic and genotypic characteristics of the medieval biovar of the plague microbe can be used in laboratory diagnostics of the plague microbe and will contribute to the study of genome changing in the process of microevolution of this highly virulent biovar.Проведен сравнительный анализ фенотипических и генотипических характеристик штаммов возбудителя чумы филогрупп 2.MED4 и 2.MED1 средневекового биовара основного подвида из эпидемически активных в ХХ веке очагов чумы Прикаспийского региона. По результатам анализа определены биохимические свойства, питательные потребности и плазмидный профиль штаммов филогрупп 2.MED4 и 2.MED1 средневекового биовара Y. pestis. Выявлена генетическая вариабельность в генах hemS, caf1М и ssaJ, ассоциированных с вирулентностью, у штаммов линии 2.MED. Полученные данные по фенотипическим и генотипическим характеристикам средневекового биовара могут найти свое применение в лабораторной диагностике чумного микроба и внесут вклад в исследование преобразований генома в процессе микроэволюции этого высоковирулентного биовара

Деконтаминация поверхностей от нуклеиновых кислот аэрозолями дезинфицирующих средств

Cross-contamination that leads to false positive results is a serious problem for laboratories using the PCR method. There are many ways to solve this problem, but none of them could be considered universal. Treatment with aerosols is the preferable method for decontamination of large areas of complex surfaces. The goal of this study was to determine effective aerosol compositions and regimens for the decontamination of nucleic acids on laboratory surfaces. The decontaminating activity of compounds that release active chlorine and active oxygen was studied using model surfaces contaminated with nucleic acids and bacteria. Effective modes of decontamination with aerosols were established by analysis of obtained experimental data. Differences between decontamination of nucleic acids and bacterial disinfection of the laboratory surfaces are shown.Важной проблемой при работе в ПЦР-лаборатории является возникновение перекрестного загрязнения, которое приводит к появлению ложноположительных результатов. Существует множество способов решения данной проблемы, однако ни один из них не является универсальным. Для деконтаминации сложных поверхностей большой площади предпочтительнее использовать аэрозольный метод обработки. Цель данного исследования заключалась в определении эффективных режимов применения дезинфицирующих средств для деконтаминации от нуклеиновых кислот аэрозольным методом. Анализ деконтаминирующей активности хлорактивных и кислородактивных соединений проводили, моделируя контаминацию поверхностей нуклеиновыми кислотами и бактериями. В процессе работы установлены эффективные режимы проведения аэрозольной деконтаминации. Показаны различия при удалении нуклеиновых кислот и бактериального загрязнения с лабораторных поверхностей

In silico identification of ivermectin as an influenza A virus nuclear export protein inhibitor

Influenza A virus (IAV) is an etiological agent infecting animals and humans that is responsible for seasonal epidemics and devastating pandemics. IAV nuclear export protein (NEP) is a multifaceted protein that plays a pivotal role in the virus life cycle. One of the most important functions of IAV NEP is to transport newly synthesized viral ribonucleoproteins from the nucleus to the cytoplasm. This function is achieved by the interaction between NEP and matrix protein 1 (M1) facilitated by Trp78 surrounded by negatively charged Glu residues in the M1 binding domain of NEP. In the present study, we targeted the IAV NEP with ivermectin. Utilizing in silico molecular docking, we tested ivermectin for its ability to bind NEP. We found that ivermectin strongly binds to NEP with an affinity of –7.3 kcal/mol. The ivermectin binding site identified in this study is located in the NEP-M1 protein interaction region. It is anticipated that blocking NEP-M1 protein interaction can have a considerably deleterious effect on IAV assembly and propagation. This study highlights the possibility of exploring ivermectin as a potential IAV NEP protein blocker, which could be an important therapeutic strategy in the treatment of influenza.Influenza A virus (IAV) is an etiological agent infecting animals and humans that is responsible for seasonal epidemics and devastating pandemics. IAV nuclear export protein (NEP) is a multifaceted protein that plays a pivotal role in the virus life cycle. One of the most important functions of IAV NEP is to transport newly synthesized viral ribonucleoproteins from the nucleus to the cytoplasm. This function is achieved by the interaction between NEP and matrix protein 1 (M1) facilitated by Trp78 surrounded by negatively charged Glu residues in the M1 binding domain of NEP. In the present study, we targeted the IAV NEP with ivermectin. Utilizing in silico molecular docking, we tested ivermectin for its ability to bind NEP. We found that ivermectin strongly binds to NEP with an affinity of –7.3 kcal/mol. The ivermectin binding site identified in this study is located in the NEP-M1 protein interaction region. It is anticipated that blocking NEP-M1 protein interaction can have a considerably deleterious effect on IAV assembly and propagation. This study highlights the possibility of exploring ivermectin as a potential IAV NEP protein blocker, which could be an important therapeutic strategy in the treatment of influenza

Современные подходы к лечению рака онколитическими вирусами

According to the World Health Organization, cancer is the second leading cause of death in the world. This serves as a powerful incentive to search for new effective cancer treatments. Development of new oncolytic viruses capable of selectively destroying cancer cells is one of the modern approaches to cancer treatment. The advantage of this method – the selective lysis of tumor cells with the help of viruses – leads to an increase in the antitumor immune response of the body, that in turn promotes the destruction of the primary tumor and its metastases. Significant progress in development of this method has been achieved in the last decade. In this review we analyze the literature data on families of oncolytic viruses that have demonstrated a positive therapeutic effect against malignant neoplasms in various localizations. We discuss the main mechanisms of the oncolytic action of viruses and assess their advantages over other methods of cancer therapy as well as the prospects for their use in clinical practice.По данным Всемирной организации здравоохранения онкологические заболевания занимают второе место по смертности в мире. Это обстоятельство является мощным стимулом для разработки новых эффективных средств лечения рака. Препараты на основе онколитических вирусов, способных избирательно уничтожать раковые клетки, являются одним из современных подходов к лечению рака. Достоинством данного метода лечения онкологических заболеваний является возможность избирательного лизиса опухолевых клеток с помощью вирусов и, как следствие, усиление противоопухолевого иммунного ответа организма, приводящего к уничтожению первичной опухоли и ее метастазов. В последнее десятилетие очевиден заметный прогресс в развитии данного метода. В настоящем обзоре мы проанализировали литературные данные по семействам вирусов, обладающих онколитическими свойствами против злокачественных новообразований различной локализации, в отношении которых был продемонстрирован положительный терапевтический эффект. Мы также рассмотрели главные механизмы онколитического действия вирусов и оценили преимущества использования вирусов перед другими методами терапии рака и перспективы их применения в клинической практике

Identification and distribution of anaerobic bacteria isolated from clinical specimens in a University Hospital: 4 years’ experience

Anaerobes, which are components of microbiota, can cause life-threatening infections. Because of their fastidious nature, they are difficult to isolate and are often overlooked. The goal of this study was to identify the anaerobic bacteria isolated from clinical specimens at the Central Laboratory of Hacettepe University Hospital in 2015-2018 and to evaluate the distribution of the isolated bacterial species among the different specimen types. The anaerobic bacteria isolated from the specimens were identified by the conventional methods and MALDI-TOF MS.Overall, 15,300 anaerobic cultures were studied. Of these, 14,434 (94.3%) were blood samples and 866 (5.7%) were other clinical specimens. A total of 138 anaerobic bacteria were isolated: 62 (44.9%) were isolated from blood samples and 76 (55.1%) from other specimens. The most isolated anaerobes from blood cultures were Bacteroides spp. (41.9%), followed by Cutibacterium acnes (25.8%) and Clostridium spp. (9.7%). The most isolated anaerobes from the other specimens were Gram-negative bacilli, including Bacteroides spp. (15.8%), Fusobacterium spp. (14.5%), Prevotella spp. (14.5%), and Porphyromonas spp. (2.6%). Anaerobic Finegoldia magna represented the major species among the isolated Gram-positive bacteria (10.5%). Anaerobic growth was observed in 0.4% of all the blood cultures and in 5.8% of the positive blood cultures. The results of our study showed that the incidence of anaerobic bacteremia was stable during the 2015-2018 period.Anaerobes, which are components of microbiota, can cause life-threatening infections. Because of their fastidious nature, they are difficult to isolate and are often overlooked. The goal of this study was to identify the anaerobic bacteria isolated from clinical specimens at the Central Laboratory of Hacettepe University Hospital in 2015-2018 and to evaluate the distribution of the isolated bacterial species among the different specimen types. The anaerobic bacteria isolated from the specimens were identified by the conventional methods and MALDI-TOF MS.Overall, 15,300 anaerobic cultures were studied. Of these, 14,434 (94.3%) were blood samples and 866 (5.7%) were other clinical specimens. A total of 138 anaerobic bacteria were isolated: 62 (44.9%) were isolated from blood samples and 76 (55.1%) from other specimens. The most isolated anaerobes from blood cultures were Bacteroides spp. (41.9%), followed by Cutibacterium acnes (25.8%) and Clostridium spp. (9.7%). The most isolated anaerobes from the other specimens were Gram-negative bacilli, including Bacteroides spp. (15.8%), Fusobacterium spp. (14.5%), Prevotella spp. (14.5%), and Porphyromonas spp. (2.6%). Anaerobic Finegoldia magna represented the major species among the isolated Gram-positive bacteria (10.5%). Anaerobic growth was observed in 0.4% of all the blood cultures and in 5.8% of the positive blood cultures. The results of our study showed that the incidence of anaerobic bacteremia was stable during the 2015-2018 period

Gut microbiome of healthy people and patients with hematological malignancies in Belarus

oai:oai.mirjournal.elpub.ru:article/98Gut microbiota plays an important role in human health and the development of various diseases. We describe the intestinal microbiome of 31 healthy individuals and 29 patients who have hematological malignancies from Belarus. Bacteria that belong to Faecalibacterium, Blautia, Bacteroides, Ruminococcus, Bifidobacterium, Prevotella, Lactobacillus, and Alistipes genera were predominant in the gut of healthy people. Based on the dominant microbiota species, two enterotype-like clusters that are driven by Bacteroides and Blautia, respectively, were identified. A significant decrease in alpha diversity and alterations in the taxonomic composition of the intestinal microbiota were observed in patients with hematological malignancies compared to healthy people. The microbiome of these patients contained a high proportion of Bacteroides, Blautia, Faecalibacterium, Lactobacillus, Prevotella, Alistipes, Enterococcus, Escherichia-Shigella, Ruminococcus gnavus group, Streptococcus, and Roseburia. An increased relative abundance of Bacteroides vulgatus, Ruminococcus torques, Veillonella, Tuzzerella, Sellimonas, and a decreased number of Akkermansia, Coprococcus, Roseburia, Agathobacter, Lachnoclostridium, and Dorea were observed in individuals with hematological malignancies. Generally, the composition of the gut microbiome in patients was more variable than that of healthy individuals, and alterations in the abundance of certain microbial taxa were individually specific.Gut microbiota plays an important role in human health and the development of various diseases. We describe the intestinal microbiome of 31 healthy individuals and 29 patients who have hematological malignancies from Belarus. Bacteria that belong to Faecalibacterium, Blautia, Bacteroides, Ruminococcus, Bifidobacterium, Prevotella, Lactobacillus, and Alistipes genera were predominant in the gut of healthy people. Based on the dominant microbiota species, two enterotype-like clusters that are driven by Bacteroides and Blautia, respectively, were identified. A significant decrease in alpha diversity and alterations in the taxonomic composition of the intestinal microbiota were observed in patients with hematological malignancies compared to healthy people. The microbiome of these patients contained a high proportion of Bacteroides, Blautia, Faecalibacterium, Lactobacillus, Prevotella, Alistipes, Enterococcus, Escherichia-Shigella, Ruminococcus gnavus group, Streptococcus, and Roseburia. An increased relative abundance of Bacteroides vulgatus, Ruminococcus torques, Veillonella, Tuzzerella, Sellimonas, and a decreased number of Akkermansia, Coprococcus, Roseburia, Agathobacter, Lachnoclostridium, and Dorea were observed in individuals with hematological malignancies. Generally, the composition of the gut microbiome in patients was more variable than that of healthy individuals, and alterations in the abundance of certain microbial taxa were individually specific

Фармакодинамическая активность нового соединения XC221GI в in vitro и in vivo моделях вирусного воспаления респираторного тракта

The viruses most commonly affecting the human respiratory tract include rhinoviruses, respiratory syncytial virus (RSV), influenza viruses, and coronaviruses (CoVs). The virus infection of the epithelial cells of the respiratory tract triggers an inflammation accompanied by the release of pro-inflammatory cytokines and chemokines including IL6, IL8(CXCL8), IL1β, and tumor necrosis factor α (TNFα). A subsequent acute inflammatory response in the lungs is accompanied by an increase in the production of cytokines and chemokines − CXCR3 receptor ligands – that are key players of acute inflammatory response that induce an influx of neutrophils and T cells into the lungs.We studied the pharmacodynamic activity of the new compound XC221GI to suppress the IL6 and IL8 of an experimental RSV infection in vitro in human lung carcinoma cells A549 and in vivo in the lungs of cotton rats. We also studied the effect of XC221GI on the production of the chemokines CXCL10, CXCL9, and CXCL11 in mouse bronchoalveolar lavage as well as on the influx of neutrophils into the mouse lungs after the intranasal administration of interferon γ (IFNγ).The obtained results demonstrate the anti-inflammatory activity of XC221GI, which suppresses the production of excessive levels of the key inflammatory markers IL6, IL8, CXCL10, CXCL9, and CXCL11 as well as the influx of neutrophils into the lungs thereby reducing lung pathology. These data confirm the effectiveness of XC221GI as a means of preventive anti-inflammatory therapy during a viral infection of the respiratory tract.Вирусы, наиболее часто поражающие респираторный тракт человека, включают риновирусы, респираторно-синцитиальный вирус (РСВ), вирусы гриппа и коронавирусы (CoV). Инфицирование вирусом эпителиальных клеток респираторного тракта запускает воспалительный процесс, сопровождающийся выбросом провоспалительных цитокинов и хемокинов, основными из которых являются интерлейкины IL6, IL8(CXCL8), IL1β и фактор некроза опухоли (tumor necrosis factor α, TNFα). Переход инфекции в фазу острой воспалительной реакции в легких сопровождается увеличением продукции цитокинов, притоком в легкие нейтрофилов и Т-клеток и индукцией хемокинов – лигандов рецептора CXCR3, – основных участников генерализованного воспаления.В настоящей работе мы изучили фармакодинамическую активность нового соединения XC221GI в отношении IL6 и IL8 в условиях экспериментальной РСВ инфекции in vitro в клетках карциномы легкого человека А549 и in vivo в легких хлопковых крыс. Мы также изучили влияние XC221GI на приток нейтрофилов в легкие мышей и индукцию хемокинов CXCL10, CXCL9 и CXCL11 в бронхоальвеолярном лаваже после интраназального введения животным интерферона γ (IFNγ).В ходе исследования была продемонстрирована противовоспалительная активность препарата XC221GI, выражающаяся в снижении избыточной продукции ключевых маркеров воспаления в легких, включающих цитокины и хемокины IL6, IL8, CXCL10, CXCL9, CXCL11 и нейтрофилы, приводя к снижению легочной патологии. Полученные результаты подтверждают эффективность препарата XC221GI в качестве средства упреждающей противовоспалительной терапии при вирусной инфекции респираторного тракта

Оценка состояния микробиома у лиц пожилого возраста с нарушениями углеводного и липидного обмена методом микробиом-ассоциированной экспосомики

A biochemical analysis of blood and a study of the chemical composition of the blood samples of 163 people 45–90 years old with type 2 diabetes mellitus and dyslipidemia was conducted. The concentrations of the following compounds in the blood were determined: fatty acids, aldehydes, and styrenes of microbial origin as well as the levels of glucose triglycerides, cholesterol, and lipids of low and high density. The chemical composition of blood was determined by gas chromatography-mass spectrometry. The concentrations of fatty acids, aldehydes, and styrenes were used to calculate the total molar concentration of chemical compounds, the concentration of octadecene aldehyde (18a), the total concentration of hydroxy acids of derivatives of the hydroxyl residue of lipid A of bacterial endotoxin (3OH-FA), and the grouped total concentrations of chemical compounds of microbial origin, which determine the representation of the main four phylotypes of the human microbiome: Actinobacteria, Bacteroidetes, Proteobacteria, and Firmicutes.As a result of the study, data were obtained on an increase in the total concentration of chemical compounds, the concentration of octadecene aldehyde, and the concentration of 3OH-FA in violation of carbohydrate metabolism by the type of diabetes mellitus type 2. There was a decrease in the representation of Bacteroidetes in violation of carbohydrate metabolism and a decrease in the representation of Proteobacteria, Firmicutes in violation of carbohydrate and lipid metabolism, and an increase in the representation of Actinobacteria in violation of lipid metabolism, including those combined with a violation of carbohydrate metabolism.In patients with type 2 diabetes mellitus and in the control group, there was an inverse correlation between the presence of Firmicutes and blood glucose levels. In the type 2 diabetes mellitus group, there was a direct correlation between the representation of Bacteroidetes and the level of triglycerides in the blood.In patients with lipid metabolism disorders, we did not reveal statistically significant changes in the concentrations of microbial markers in the blood of patients nor statistically significant correlations between the biochemical blood parameters and the representation of microbiome phylotypes.Проведены биохимический анализ крови и исследование химического состава образцов крови 163 пациентов в возрасте 45–90 лет с сахарным диабетом 2-го типа и дислипидемиями. В крови определяли концентрации жирных кислот, альдегидов, стиролов, имеющих микробное происхождение, а также уровни глюкозы, триглицеридов, холестерина, липидов низкой и высокой плотности. Химический состав крови определяли методом газовой хромато-масс-спектрометрии. По концентрациям жирных кислот, альдегидов, стиролов рассчитывали суммарную молярную концентрацию малых молекул микробного происхождения (Small molecules originating from microbes, SMOM), концентрацию октадеценового альдегида (18a), суммарную концентрацию гидроксикислот, производных гидроксильного остатка липида А, бактериального эндотоксина (3OH-FA) и сгруппированные суммарные концентрации химических соединений микробного происхождения, определяющих представительство основных четырех филотипов микробиома человека: Actinobacteria, Bacteroidetes, Proteobacteria, Firmicutes.В  результате исследования были получены данные об увеличении суммарной концентрации химических соединений, концентрации октадеценового альдегида и концентрации 3OH-FA у пациентов при нарушении углеводного обмена по типу сахарного диабета 2-го типа. Снижение представленности Bacteroidetes отмечали при нарушении углеводного обмена и снижение представленности Proteobacteria и Firmicutes – при нарушении углеводного и липидного обменов, а также увеличение представленности Actinobacteria – при нарушении липидного обмена, в том числе сочетанного с нарушением углеводного обмена. У пациентов с сахарным диабетом 2-го типа и в контрольной группе отмечена обратная корреляция между представленностью Firmicutes и уровнем глюкозы в крови. В группе пациентов с сахарным диабетом 2-го типа отмечена прямая корреляция представленности Bacteroidetes и уровня триглицеридов в крови.При нарушениях липидного обмена не выявлено ни статистически значимых изменений концентраций микробных маркеров в крови пациентов, ни статистически значимых корреляционных связей биохимических параметров крови и представленности филотипов микробиом

Three cases of Actinomyces isolation from the eye lesions of patients with a chronic and recurrent ophthalmic infection

Actinomycosis is an indolent, slowly progressive infection caused by Gram-positive facultative anaerobic bacteria from the genus Actinomyces. These bacteria have been reported as a cause of ophthalmic infections such as endophthalmitis, keratitis, and canaliculitis. The objective of the present study was to investigate the pattern and antibiotic sensitivity profile of anaerobes isolated from lesions in the medial canthus of the eye.Three pus aspirate samples (from eye) were delivered to a microbiology laboratory in a strict anaerobic condition in Robertson Cooked Meat media (RCM). The samples were inoculated on Blood Agar and incubated anaerobically in a Gas Pack Jar incubator at 5%-10% CO2 and in aerobic condition at 37°C. Pure colonies isolated on anaerobically incubated plates were identified by the VITEK® 2 COMPACT system. Antibiotic sensitivity testing was conducted using an Epsilometer-strip test.Three isolates identified and confirmed with the help of VITEK® 2 were Actinomyces israelii, Actinomyces odontolyticus, and Actinomyces meyeri. All three species of Actinomyces were sensitive to Vancomycin, Moxifloxacin, and Imipenem, but they were resistant to Metronidazole.Since there have been several cases of anaerobic ophthalmic infections reported to date, samples from patients with chronic eye infections should be analyzed for anaerobic culture for correct diagnosis and proper treatment. Moxifloxacin but not Metroni­dazole is a suitable drug for the treatment of anaerobic eye infection. Actinomycosis is an indolent, slowly progressive infection caused by Gram-positive facultative anaerobic bacteria from the genus Actinomyces. These bacteria have been reported as a cause of ophthalmic infections such as endophthalmitis, keratitis, and canaliculitis. The objective of the present study was to investigate the pattern and antibiotic sensitivity profile of anaerobes isolated from lesions in the medial canthus of the eye.Three pus aspirate samples (from eye) were delivered to a microbiology laboratory in a strict anaerobic condition in Robertson Cooked Meat media (RCM). The samples were inoculated on Blood Agar and incubated anaerobically in a Gas Pack Jar incubator at 5%-10% CO2 and in aerobic condition at 37°C. Pure colonies isolated on anaerobically incubated plates were identified by the VITEK® 2 COMPACT system. Antibiotic sensitivity testing was conducted using an Epsilometer-strip test.Three isolates identified and confirmed with the help of VITEK® 2 were Actinomyces israelii, Actinomyces odontolyticus, and Actinomyces meyeri. All three species of Actinomyces were sensitive to Vancomycin, Moxifloxacin, and Imipenem, but they were resistant to Metronidazole.Since there have been several cases of anaerobic ophthalmic infections reported to date, samples from patients with chronic eye infections should be analyzed for anaerobic culture for correct diagnosis and proper treatment. Moxifloxacin but not Metroni­dazole is a suitable drug for the treatment of anaerobic eye infection.