Pub Date : 2023-01-01DOI: 10.20953/1729-9225-2023-2-57-63
V. Gorodin, D. Moysova, I. I. Chuprov
This review shows the current literature data on the delayed consequences of COVID-19 for the hemostasis. The pathogenesis, epidemiology, clinical manifestations, diagnostics, and possibilities of correction of hemostasis disorders are presented. In the context of declining mortality from COVID-19, the long-term multisystem consequences of the disease, which significantly affect the life quality oof convalescents are gradually becoming the main health problem of all states. The main mechanism for the occurrence of post-COVID syndrome is persistent inflammation, which is an important part of endotheliopathy. Most of the modern studies indicate a low incidence of VTE (0.8–1.6%) and arterial thrombosis (0.75%) in the post-COVID period. Laboratory data in the post-COVID period confirm endothelial dysfunction and the persisting prothrombotic phenotype of hemostasis disorder. The strategy of selective prolonged thromboprophylaxis of COVID-19 convalescents discharged from the hospital is justified, but the duration and criteria for the sufficiency of thromboprophylaxis are unknown. The tactics of endothelial protection are recognized as pathogenetically significant, but there is no reliable evidence base for the use of sulodexide in the post-COVID period. Key words: post-COVID syndrome, hemostasis, thrombosis, anticoagulants, sulodexide
{"title":"Hemostasis in the post-COVID period","authors":"V. Gorodin, D. Moysova, I. I. Chuprov","doi":"10.20953/1729-9225-2023-2-57-63","DOIUrl":"https://doi.org/10.20953/1729-9225-2023-2-57-63","url":null,"abstract":"This review shows the current literature data on the delayed consequences of COVID-19 for the hemostasis. The pathogenesis, epidemiology, clinical manifestations, diagnostics, and possibilities of correction of hemostasis disorders are presented. In the context of declining mortality from COVID-19, the long-term multisystem consequences of the disease, which significantly affect the life quality oof convalescents are gradually becoming the main health problem of all states. The main mechanism for the occurrence of post-COVID syndrome is persistent inflammation, which is an important part of endotheliopathy. Most of the modern studies indicate a low incidence of VTE (0.8–1.6%) and arterial thrombosis (0.75%) in the post-COVID period. Laboratory data in the post-COVID period confirm endothelial dysfunction and the persisting prothrombotic phenotype of hemostasis disorder. The strategy of selective prolonged thromboprophylaxis of COVID-19 convalescents discharged from the hospital is justified, but the duration and criteria for the sufficiency of thromboprophylaxis are unknown. The tactics of endothelial protection are recognized as pathogenetically significant, but there is no reliable evidence base for the use of sulodexide in the post-COVID period. Key words: post-COVID syndrome, hemostasis, thrombosis, anticoagulants, sulodexide","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67729345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.20953/1729-9225-2023-2-64-81
S. Sitkin, E. Avalueva, I. Bakulin, M. I. Skalinskaya, S. Vorobyev, E. Pavlova, A. Khavkin
Inflammatory bowel disease (IBD) is a group of phenotypically similar diseases characterized by multiple organ damage with predominant localization in the gastrointestinal tract and conditionally divided into two nosologies, ulcerative colitis (UC) and Crohn's disease (CD). IBD is closely associated with taxonomic and functional dysbiosis, however, to date, no study has confirmed that a single specific microorganism is the direct cause of IBD according to Koch’s postulates. The complexity of the etiology and pathogenesis of IBD determines the high interest in studying the infectious factor, not as the only causally significant factor, but as a trigger and/or comorbid one. The review summarizes current data on the involvement of the most important microorganisms (pathogens, opportunistic microorganisms, and pathobionts) in the pathogenesis of UC and CD and considers their possible role in the induction, progression, and course of IBD. A possible relationship between IBD and bacteria belonging to the phyla Pseudomonadota ( Proteobacteria), Bacillota ( Firmicutes), Actinomycetota ( Actinobacteria), and Spirochaetota, archaea, fungi, and eukaryotic viruses is discussed. Bacteria such as adhesive-invasive strains of Escherichia coli (AIEC), Salmonella enterica Typhimurium, Campylobacter jejuni, Campylobacter concisus, enterohepatic species of Helicobacter (including Helicobacter bilis), Proteus spp., Aeromonas spp., Klebsiella pneumoniae, Yersinia enterocolitica, Clostridioides difficile, Enterococcus spp., Staphylococcus aureus, Mycobacterium avium subsp. paratuberculosis and Brachyspira spp. The involvement of methanogenic archaea, such as Methanobrevibacter smithii and Methanosphaera stadtmanae, in immunoinflammatory processes in IBD has been shown. The pro-inflammatory role of intestinal fungi Candida albicans, which produces the cytolytic toxin candidalysin, Candida tropicalis, which forms polymicrobial biofilms, and Debaryomyces hansenii, has been revealed. The role of eukaryotic viruses such as herpesviruses (cytomegalovirus, Epstein–Barr virus, human herpesvirus 6), enteropathogenic viruses (norovirus), enterovirus B, hepatitis B virus (Orthohepadnavirus) in the development of IBD is discussed. Particular attention is paid to the possible role of the SARS-CoV-2 (COVID-19) virus as a trigger of IBD. Key words: inflammatory bowel disease, infections, archaea, bacteria, viruses, fungi, dysbiosis, gut microbiota
{"title":"The role of bacterial, fungal, and viral infections in the pathogenesis of inflammatory bowel disease","authors":"S. Sitkin, E. Avalueva, I. Bakulin, M. I. Skalinskaya, S. Vorobyev, E. Pavlova, A. Khavkin","doi":"10.20953/1729-9225-2023-2-64-81","DOIUrl":"https://doi.org/10.20953/1729-9225-2023-2-64-81","url":null,"abstract":"Inflammatory bowel disease (IBD) is a group of phenotypically similar diseases characterized by multiple organ damage with predominant localization in the gastrointestinal tract and conditionally divided into two nosologies, ulcerative colitis (UC) and Crohn's disease (CD). IBD is closely associated with taxonomic and functional dysbiosis, however, to date, no study has confirmed that a single specific microorganism is the direct cause of IBD according to Koch’s postulates. The complexity of the etiology and pathogenesis of IBD determines the high interest in studying the infectious factor, not as the only causally significant factor, but as a trigger and/or comorbid one. The review summarizes current data on the involvement of the most important microorganisms (pathogens, opportunistic microorganisms, and pathobionts) in the pathogenesis of UC and CD and considers their possible role in the induction, progression, and course of IBD. A possible relationship between IBD and bacteria belonging to the phyla Pseudomonadota ( Proteobacteria), Bacillota ( Firmicutes), Actinomycetota ( Actinobacteria), and Spirochaetota, archaea, fungi, and eukaryotic viruses is discussed. Bacteria such as adhesive-invasive strains of Escherichia coli (AIEC), Salmonella enterica Typhimurium, Campylobacter jejuni, Campylobacter concisus, enterohepatic species of Helicobacter (including Helicobacter bilis), Proteus spp., Aeromonas spp., Klebsiella pneumoniae, Yersinia enterocolitica, Clostridioides difficile, Enterococcus spp., Staphylococcus aureus, Mycobacterium avium subsp. paratuberculosis and Brachyspira spp. The involvement of methanogenic archaea, such as Methanobrevibacter smithii and Methanosphaera stadtmanae, in immunoinflammatory processes in IBD has been shown. The pro-inflammatory role of intestinal fungi Candida albicans, which produces the cytolytic toxin candidalysin, Candida tropicalis, which forms polymicrobial biofilms, and Debaryomyces hansenii, has been revealed. The role of eukaryotic viruses such as herpesviruses (cytomegalovirus, Epstein–Barr virus, human herpesvirus 6), enteropathogenic viruses (norovirus), enterovirus B, hepatitis B virus (Orthohepadnavirus) in the development of IBD is discussed. Particular attention is paid to the possible role of the SARS-CoV-2 (COVID-19) virus as a trigger of IBD. Key words: inflammatory bowel disease, infections, archaea, bacteria, viruses, fungi, dysbiosis, gut microbiota","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67729399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.20953/1729-9225-2023-2-35-40
Y. Kulakov, O. Burgasova, A. Dalgatova, R. Khodzhibekov
Brucellosis is a zoonotic infection characterized by variable clinical manifestations, a variety of transmission routes, chronic inflammation, and risk of disability. Brucellosis remains a problem of practical healthcare in Russia, especially in endemic regions. Laboratory tests for brucellosis diagnosis are rarely used together, which prevents objective comparison of their effectiveness for different clinical forms of the disease. In this study, we analyzed different laboratory methods for comprehensive diagnosis of various clinical forms of brucellosis. Objective. To compare different laboratory methods for the diagnosis of various clinical forms of brucellosis. Materials and methods. We tested serum from 1049 individuals collected between 2005 and 2022. Samples were analyzed using agglutination reaction in tubes (Wright reaction; WR), on slides (Huddleson reaction; HR), Coombs test (CT), enzymelinked immunosorbent assay (ELISA), and real-time polymerase chain reaction (PCR) for BCSP31. We also performed retrospective analysis of 325 patient records. Of them, 110 patients (34%) had acute brucellosis, whereas 215 patients (66%) had chronic brucellosis. The control group comprised 604 individuals (with no clinical, epidemiological signs tested negative for brucellosis). Results. We analyzed 325 brucellosis patients (including 110 with acute disease, 215 with chronic disease, and 120 with no clinical manifestations) and 604 healthy controls. The sensitivity of PCR in acute and chronic disease was 94% and 32%, respectively. The specificity of PCR was 99.7%. ELISA demonstrated 92% and 86% sensitivity in acute and chronic disease, respectively, with a specificity of 98%. The negative and positive prognostic value for ELIZA and PCR were 95% and 96%, 83% and 99% respectively, suggesting similar effectiveness and accuracy of these methods. The sensitivity of traditional serological tests in acute disease was 75%, 62%, and 56.3% for RH, WR, and CT, respectively. In patients with chronic brucellosis, their sensitivity did not exceed 60%. Specificity of WR and CT was 97% in chronic disease, while it of RH dropped to 83%. Conclusion. PCR and ELISA ensured high diagnostic effectiveness and accuracy in assessing the activity of infection and diagnosis of brucellosis clinical forms, as well as in screening among vulnerable individuals. Traditional serological tests, despite their lower sensitivity, confirm acute disease and need for comprehensive laboratory diagnostics of brucellosis patients. Key words: brucellosis, diagnostic methods, enzyme-linked immunosorbent assay, polymerase chain reaction, Wright reaction, Huddleson reaction, Coombs test
{"title":"Comparison of laboratory methods for the diagnosis of different clinical forms of brucellosis","authors":"Y. Kulakov, O. Burgasova, A. Dalgatova, R. Khodzhibekov","doi":"10.20953/1729-9225-2023-2-35-40","DOIUrl":"https://doi.org/10.20953/1729-9225-2023-2-35-40","url":null,"abstract":"Brucellosis is a zoonotic infection characterized by variable clinical manifestations, a variety of transmission routes, chronic inflammation, and risk of disability. Brucellosis remains a problem of practical healthcare in Russia, especially in endemic regions. Laboratory tests for brucellosis diagnosis are rarely used together, which prevents objective comparison of their effectiveness for different clinical forms of the disease. In this study, we analyzed different laboratory methods for comprehensive diagnosis of various clinical forms of brucellosis. Objective. To compare different laboratory methods for the diagnosis of various clinical forms of brucellosis. Materials and methods. We tested serum from 1049 individuals collected between 2005 and 2022. Samples were analyzed using agglutination reaction in tubes (Wright reaction; WR), on slides (Huddleson reaction; HR), Coombs test (CT), enzymelinked immunosorbent assay (ELISA), and real-time polymerase chain reaction (PCR) for BCSP31. We also performed retrospective analysis of 325 patient records. Of them, 110 patients (34%) had acute brucellosis, whereas 215 patients (66%) had chronic brucellosis. The control group comprised 604 individuals (with no clinical, epidemiological signs tested negative for brucellosis). Results. We analyzed 325 brucellosis patients (including 110 with acute disease, 215 with chronic disease, and 120 with no clinical manifestations) and 604 healthy controls. The sensitivity of PCR in acute and chronic disease was 94% and 32%, respectively. The specificity of PCR was 99.7%. ELISA demonstrated 92% and 86% sensitivity in acute and chronic disease, respectively, with a specificity of 98%. The negative and positive prognostic value for ELIZA and PCR were 95% and 96%, 83% and 99% respectively, suggesting similar effectiveness and accuracy of these methods. The sensitivity of traditional serological tests in acute disease was 75%, 62%, and 56.3% for RH, WR, and CT, respectively. In patients with chronic brucellosis, their sensitivity did not exceed 60%. Specificity of WR and CT was 97% in chronic disease, while it of RH dropped to 83%. Conclusion. PCR and ELISA ensured high diagnostic effectiveness and accuracy in assessing the activity of infection and diagnosis of brucellosis clinical forms, as well as in screening among vulnerable individuals. Traditional serological tests, despite their lower sensitivity, confirm acute disease and need for comprehensive laboratory diagnostics of brucellosis patients. Key words: brucellosis, diagnostic methods, enzyme-linked immunosorbent assay, polymerase chain reaction, Wright reaction, Huddleson reaction, Coombs test","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67729417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.20953/1729-9225-2022-2-33-40
A. E. Goncharov, D. Azarov, A. Mokhov, A. Pochtovyi, D. D. Kustova, V. Gushchin, E. Lebedeva, V. Kolodzhieva, A. Kireeva, L. Kraeva, S. Dolinny, O. Burgasova, A.R. Goncharova, E. Belková, A. Dmitriev
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
{"title":"Characteristics of hypervirulent multi-drug resistant Klebsiella pneumoniae strains in inpatients with severe COVID-19","authors":"A. E. Goncharov, D. Azarov, A. Mokhov, A. Pochtovyi, D. D. Kustova, V. Gushchin, E. Lebedeva, V. Kolodzhieva, A. Kireeva, L. Kraeva, S. Dolinny, O. Burgasova, A.R. Goncharova, E. Belková, A. Dmitriev","doi":"10.20953/1729-9225-2022-2-33-40","DOIUrl":"https://doi.org/10.20953/1729-9225-2022-2-33-40","url":null,"abstract":"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","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67727764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.20953/1729-9225-2022-2-6-15
A. Gorelov, A. Malyavin, E. Antonova, T.A. Pobedinskaya, А.А. Globenko, A. Kapashin, M. Bagaeva
COVID-19 is known to have two main clinical periods: active viral replication followed by immune dysregulation or hyperinflammatory response. Therefore, early initiation of antiviral therapy that limits viral replication and prevents lifethreatening complication appears to be rational. Ingavirin® is one of well-known antiviral drugs proved to be effective against a wide range of respiratory viruses in adults and children. The efficacy of Ingavirin® against the highly pathogenic SARS-CoV was demonstrated in preclinical studies even before the COVID-19 pandemic. Thus, preclinical studies developed the grounds for further assessment of its clinical efficacy in COVID-19 patients. Objective. To conduct phase III clinical trial to evaluate the efficacy and safety of Ingavirin® (90-mg capsules) in COVID-19 patients during their outpatient treatment. Patients and methods. A total of 234 candidates of both sexes aged 18 to 75 years with laboratory confirmed COVID-19 were screened. Of them, 233 patients were recruited and randomized in one of the two groups: Ingavirin® or placebo. Maximum treatment duration was 7 days. After its completion, the patients were followed up for 21±1 days. Results. Ingavirin® demonstrated the superior efficacy over placebo for COVID-19 with respect to clinical recovery. Patients in the experimental group demonstrated faster clinical recovery (by 47.8 h) and alleviation of intoxication and individual catarrhal symptoms. Ingavirin® also demonstrated a good safety profile as shown by the analysis of its side effects, tolerability, and laboratory parameters of the patients. Key words: imidazolyl ethanamide pentandioic acid, Ingavirin, new coronavirus infection, antiviral therapy, COVID-19, SARS-CoV-2
{"title":"Efficacy and safety of imidazolyl ethanamide pentandioic acid for COVID-19: a multicenter, randomized, double-blind, placebo-controlled clinical trial","authors":"A. Gorelov, A. Malyavin, E. Antonova, T.A. Pobedinskaya, А.А. Globenko, A. Kapashin, M. Bagaeva","doi":"10.20953/1729-9225-2022-2-6-15","DOIUrl":"https://doi.org/10.20953/1729-9225-2022-2-6-15","url":null,"abstract":"COVID-19 is known to have two main clinical periods: active viral replication followed by immune dysregulation or hyperinflammatory response. Therefore, early initiation of antiviral therapy that limits viral replication and prevents lifethreatening complication appears to be rational. Ingavirin® is one of well-known antiviral drugs proved to be effective against a wide range of respiratory viruses in adults and children. The efficacy of Ingavirin® against the highly pathogenic SARS-CoV was demonstrated in preclinical studies even before the COVID-19 pandemic. Thus, preclinical studies developed the grounds for further assessment of its clinical efficacy in COVID-19 patients. Objective. To conduct phase III clinical trial to evaluate the efficacy and safety of Ingavirin® (90-mg capsules) in COVID-19 patients during their outpatient treatment. Patients and methods. A total of 234 candidates of both sexes aged 18 to 75 years with laboratory confirmed COVID-19 were screened. Of them, 233 patients were recruited and randomized in one of the two groups: Ingavirin® or placebo. Maximum treatment duration was 7 days. After its completion, the patients were followed up for 21±1 days. Results. Ingavirin® demonstrated the superior efficacy over placebo for COVID-19 with respect to clinical recovery. Patients in the experimental group demonstrated faster clinical recovery (by 47.8 h) and alleviation of intoxication and individual catarrhal symptoms. Ingavirin® also demonstrated a good safety profile as shown by the analysis of its side effects, tolerability, and laboratory parameters of the patients. Key words: imidazolyl ethanamide pentandioic acid, Ingavirin, new coronavirus infection, antiviral therapy, COVID-19, SARS-CoV-2","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67727776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.20953/1729-9225-2022-1-16-22
O. Tumash, A. M. Karamyshau, I. Stoma, M. N. Menshakova, I. O. Vakulchik
Objective. To estimate efficiency and safety of remdesivir in treating new coronavirus infection in pregnant. Materials and methods. A retrospective cohort study including 61 medical patient’s records who underwent COVID-19 and being pregnant more than 20 weeks was conducted. Medical case histories were divided into 2 groups: the main one with the use of remdesivir treatment (n = 35) and control one (n = 26) without it. The groups were representative by age, anthropometric data and comorbidity (p > 0.05). Results. The use of remdesivir in pregnant patients with COVID-19 causes a reduction in fever by 15% and achievement of target saturation values in 94.3% of cases, reduces С-reaction protein (CRP) levels by 3.5 times, D-dimer by 2.6, Lactat Dehydrogenase (LDG) by 1.4 times on 5th day from the moment of hospitalization, reduces its duration by 30.8%, does not affect the course of pregnancy and the frequency of Cesarean section. Conclusion. The use of remdesivir in the treatment of COVID-19 in pregnant patients with a gestation period of more than 20 weeks is effective, as evidenced by the shortening of the fever period, the duration of hospitalization, improving oxygenation, reduction of laboratory markers "cytokine storm" in blood levels and safe due to the lack of impact on pregnancy and delivery strategy. Key words: СOVID-19, cytokine storm, laboratory criteria, pregnancy, remdesivir
{"title":"Remdesivir influence on course of new coronaviral infection in pregnant","authors":"O. Tumash, A. M. Karamyshau, I. Stoma, M. N. Menshakova, I. O. Vakulchik","doi":"10.20953/1729-9225-2022-1-16-22","DOIUrl":"https://doi.org/10.20953/1729-9225-2022-1-16-22","url":null,"abstract":"Objective. To estimate efficiency and safety of remdesivir in treating new coronavirus infection in pregnant. Materials and methods. A retrospective cohort study including 61 medical patient’s records who underwent COVID-19 and being pregnant more than 20 weeks was conducted. Medical case histories were divided into 2 groups: the main one with the use of remdesivir treatment (n = 35) and control one (n = 26) without it. The groups were representative by age, anthropometric data and comorbidity (p > 0.05). Results. The use of remdesivir in pregnant patients with COVID-19 causes a reduction in fever by 15% and achievement of target saturation values in 94.3% of cases, reduces С-reaction protein (CRP) levels by 3.5 times, D-dimer by 2.6, Lactat Dehydrogenase (LDG) by 1.4 times on 5th day from the moment of hospitalization, reduces its duration by 30.8%, does not affect the course of pregnancy and the frequency of Cesarean section. Conclusion. The use of remdesivir in the treatment of COVID-19 in pregnant patients with a gestation period of more than 20 weeks is effective, as evidenced by the shortening of the fever period, the duration of hospitalization, improving oxygenation, reduction of laboratory markers \"cytokine storm\" in blood levels and safe due to the lack of impact on pregnancy and delivery strategy. Key words: СOVID-19, cytokine storm, laboratory criteria, pregnancy, remdesivir","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67727685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.20953/1729-9225-2022-1-64-73
S. Malov, L. Orlova, L. A. Stepanenko, O. Ogarkov, I. Malov, N. D. Yushchuk
Objective. To determine environmental and genetic factors associated with fibrosis progression after virus elimination as a result of direct-acting antiviral therapy by follow-up dispensary observation of patients with chronic hepatitis C with moderate and severe liver fibrosis (F2–F3 according to the METAVIR scoring system). Patients and methods. This study included 301 patients (166 men and 135 women) aged 20-64 years with chronic hepatitis C virus (HCV). A sustained virologic response was achieved in all patients after therapy with direct-acting antiviral agents. Patients were followed up for an average of 38 weeks (16–64). Patients were divided into two groups in order to perform comparative evaluation: group I included 257 patients with regression of liver fibrosis and group II – 44 patients with progression of liver fibrosis. Questionnaire and clinical and laboratory data were assessed. In addition, genetic studies of 24 singlenucleotide polymorphisms of genes involved in intracellular immune signaling pathway activation, interferon synthesis, metabolic regulation and cell proliferation were performed in both groups. Results. It was revealed that validated predictors of liver fibrosis progression in patients with chronic HCV after successful virus elimination as a result of therapy with direct-acting antiviral agents are the presence of concomitant type 2 diabetes mellitus, low ALT activity and serum osteopontin levels over 80 ng/mL at the beginning of therapy. Genetic predisposition to liver fibrosis progression is mediated by carriage of the AA genotype of HNF4α rs4812829 (OR = 3.55; 95% CI 1.21–10.41; p = 0.015). Additionally, the G-allele of NAT2 rs1495741, which marks fast xenobiotic acetylation, was found to have protective properties in the dominant genetic model. Carriers of GG- and GA-genotypes had an almost 2-fold lower risk of liver fibrosis progression after antiviral therapy than AA-genotype carriers (OR = 0.49; 95% CI 0.25–0.94; p = 0.029). Conclusion. The risk after successful hepatitis C virus elimination is significantly higher in patients with concomitant type 2 diabetes mellitus. ALT activity and serum osteopontin levels at the beginning of therapy can be estimated as predictors of liver fibrosis progression among laboratory parameters. Moreover, some genetic markers in the form of single-nucleotide polymorphisms of the HNF4α and NAT2 genes were established, which can be used to predict the development of liver fibrosis in patients with hepatitis C after therapy with direct-acting antiviral agents. Key words: hepatitis C, liver fibrosis, predictors, risk factors, diabetes mellitus, osteopontin, single-nucleotide polymorphisms, HNF4α gene, NAT2 gene
目标。通过对慢性丙型肝炎合并中重度肝纤维化(METAVIR评分系统F2-F3)患者的随访药房观察，确定直接作用抗病毒治疗消除病毒后纤维化进展的环境和遗传因素。患者和方法。本研究纳入了301例年龄在20-64岁的慢性丙型肝炎病毒(HCV)患者(166名男性和135名女性)。所有患者在接受直接抗病毒药物治疗后均取得了持续的病毒学应答。患者平均随访38周(16 ~ 64周)。将患者分为两组进行比较评价:I组257例肝纤维化消退患者，II组44例肝纤维化进展患者。对问卷调查、临床和实验室数据进行评估。此外，对两组小鼠细胞内免疫信号通路激活、干扰素合成、代谢调节和细胞增殖相关基因的24个单核苷酸多态性进行遗传研究。结果。结果显示，在直接抗病毒药物治疗成功消除病毒后，慢性HCV患者肝纤维化进展的有效预测因素是伴有2型糖尿病、低ALT活性和治疗开始时血清骨桥蛋白水平超过80 ng/mL。携带HNF4α rs4812829 AA基因型介导肝纤维化进展的遗传易感性(OR = 3.55;95% ci 1.21-10.41;P = 0.015)。此外，在显性遗传模型中，发现NAT2 rs1495741的g等位基因具有快速外源乙酰化的保护特性。GG-和ga基因型携带者在抗病毒治疗后肝纤维化进展的风险比aa基因型携带者低近2倍(OR = 0.49;95% ci 0.25-0.94;P = 0.029)。结论。伴有2型糖尿病的丙型肝炎病毒清除成功后的风险明显更高。治疗开始时ALT活性和血清骨桥蛋白水平可作为肝纤维化进展的预测指标。此外，还建立了HNF4α和NAT2基因单核苷酸多态性的遗传标记，可用于预测直接作用抗病毒药物治疗后丙型肝炎患者肝纤维化的发展。关键词:丙型肝炎，肝纤维化，预测因素，危险因素，糖尿病，骨桥蛋白，单核苷酸多态性，HNF4α基因，NAT2基因
{"title":"Evaluation of predictors of liver fibrosis progression in patients with hepatitis C after successful virus elimination","authors":"S. Malov, L. Orlova, L. A. Stepanenko, O. Ogarkov, I. Malov, N. D. Yushchuk","doi":"10.20953/1729-9225-2022-1-64-73","DOIUrl":"https://doi.org/10.20953/1729-9225-2022-1-64-73","url":null,"abstract":"Objective. To determine environmental and genetic factors associated with fibrosis progression after virus elimination as a result of direct-acting antiviral therapy by follow-up dispensary observation of patients with chronic hepatitis C with moderate and severe liver fibrosis (F2–F3 according to the METAVIR scoring system). Patients and methods. This study included 301 patients (166 men and 135 women) aged 20-64 years with chronic hepatitis C virus (HCV). A sustained virologic response was achieved in all patients after therapy with direct-acting antiviral agents. Patients were followed up for an average of 38 weeks (16–64). Patients were divided into two groups in order to perform comparative evaluation: group I included 257 patients with regression of liver fibrosis and group II – 44 patients with progression of liver fibrosis. Questionnaire and clinical and laboratory data were assessed. In addition, genetic studies of 24 singlenucleotide polymorphisms of genes involved in intracellular immune signaling pathway activation, interferon synthesis, metabolic regulation and cell proliferation were performed in both groups. Results. It was revealed that validated predictors of liver fibrosis progression in patients with chronic HCV after successful virus elimination as a result of therapy with direct-acting antiviral agents are the presence of concomitant type 2 diabetes mellitus, low ALT activity and serum osteopontin levels over 80 ng/mL at the beginning of therapy. Genetic predisposition to liver fibrosis progression is mediated by carriage of the AA genotype of HNF4α rs4812829 (OR = 3.55; 95% CI 1.21–10.41; p = 0.015). Additionally, the G-allele of NAT2 rs1495741, which marks fast xenobiotic acetylation, was found to have protective properties in the dominant genetic model. Carriers of GG- and GA-genotypes had an almost 2-fold lower risk of liver fibrosis progression after antiviral therapy than AA-genotype carriers (OR = 0.49; 95% CI 0.25–0.94; p = 0.029). Conclusion. The risk after successful hepatitis C virus elimination is significantly higher in patients with concomitant type 2 diabetes mellitus. ALT activity and serum osteopontin levels at the beginning of therapy can be estimated as predictors of liver fibrosis progression among laboratory parameters. Moreover, some genetic markers in the form of single-nucleotide polymorphisms of the HNF4α and NAT2 genes were established, which can be used to predict the development of liver fibrosis in patients with hepatitis C after therapy with direct-acting antiviral agents. Key words: hepatitis C, liver fibrosis, predictors, risk factors, diabetes mellitus, osteopontin, single-nucleotide polymorphisms, HNF4α gene, NAT2 gene","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67727741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.20953/1729-9225-2022-1-74-81
A. Savchenko, E. P. Tikhonova, V. Belenjuk, A. Anisimova, A. Borisov
Objective. To analyze the phenotype of B-lymphocytes in patients with chronic infection with hepatitis C virus (HCV) before and after treatment with direct-acting antivirals (DAAs) depending on the virus genotype. Patients and methods. This open-label clinical and immunological study included 111 HCV patients with a mean age of 43.4 ± 8.6 years who received DAAs: Sofosbuvir (400 mg) and Velpatasvir (100 mg) once a day for 12 weeks. We assessed the phenotypic diversity of B-lymphocytes in peripheral blood of HCV patients during therapy and after its completion depending on the virus genotype. Results. Prior to DAA initiation, HCV patients demonstrated elevated count of CD19+CD5+CD27+ B cells and CD23+ B cells along with a decreased count of CD19+CD5–CD27+ B cells compared to controls. After therapy with DAAs, HCV patients continued to have increased proportion of CD19+CD5+CD27+ cells and reduced proportion of CD19+CD5–CD27+ cells. Conclusion. The pretreatment phenotypic diversity of peripheral B cells in HCV patents did not depend on the HCV genotype and was characterized by increased levels of B1 memory cells and activated B cells of the main subpopulations, along with a decreased level of B2 memory cells. The changes in the count of different B-cell subpopulations after DAA therapy depend on HCV genotype and might be associated with the rate of virus elimination. Key words: B-lymphocytes, immune system, direct-acting antivirals, chronic hepatitis C
{"title":"Phenotypic diversity of B cells in patients with chronic hepatitis C and its association with virus genotype (before and after therapy with direct-acting antivirals)","authors":"A. Savchenko, E. P. Tikhonova, V. Belenjuk, A. Anisimova, A. Borisov","doi":"10.20953/1729-9225-2022-1-74-81","DOIUrl":"https://doi.org/10.20953/1729-9225-2022-1-74-81","url":null,"abstract":"Objective. To analyze the phenotype of B-lymphocytes in patients with chronic infection with hepatitis C virus (HCV) before and after treatment with direct-acting antivirals (DAAs) depending on the virus genotype. Patients and methods. This open-label clinical and immunological study included 111 HCV patients with a mean age of 43.4 ± 8.6 years who received DAAs: Sofosbuvir (400 mg) and Velpatasvir (100 mg) once a day for 12 weeks. We assessed the phenotypic diversity of B-lymphocytes in peripheral blood of HCV patients during therapy and after its completion depending on the virus genotype. Results. Prior to DAA initiation, HCV patients demonstrated elevated count of CD19+CD5+CD27+ B cells and CD23+ B cells along with a decreased count of CD19+CD5–CD27+ B cells compared to controls. After therapy with DAAs, HCV patients continued to have increased proportion of CD19+CD5+CD27+ cells and reduced proportion of CD19+CD5–CD27+ cells. Conclusion. The pretreatment phenotypic diversity of peripheral B cells in HCV patents did not depend on the HCV genotype and was characterized by increased levels of B1 memory cells and activated B cells of the main subpopulations, along with a decreased level of B2 memory cells. The changes in the count of different B-cell subpopulations after DAA therapy depend on HCV genotype and might be associated with the rate of virus elimination. Key words: B-lymphocytes, immune system, direct-acting antivirals, chronic hepatitis C","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67727845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.20953/1729-9225-2022-3-129-132
P. Bogomolov, A. O. Bueverov, E. Bueverova, A.A. Кhvan, I. Maev, M.V. Arapova, N.A. Shub, E. A. Isaeva, S. V. Koblov
The lack of effective etiotropic therapy is a serious challenge in the treatment of patients with COVID-19. The recent emergence of a new class of medications neutralizing monoclonal antibodies against the SARS-CoV-2 spike protein allows to partially solve this problem. This article presents a clinical case of a patient with an increased risk of COVID-19 complications (paroxysmal atrial fibrillation, atherogenic dyslipidemia, impaired carbohydrate tolerance) who was treated with 600 mg casirivimab and 600 mg imdevimab by intravenous infusion. A significant improvement in the patient's well-being was noted within the first 24 hours: normalization of body temperature, stool, reduction of weakness, disappearance of arthralgia and myalgia. After 48 hours, a negative test result for SARS-CoV-2 RNA was obtained, which altogether made it possible to state the recovery. There were no adverse events during and after therapy. The casirivimab and imdevimab monoclonal antibody combination may be considered as a promising etiotropic treatment for COVID-19. Key words: COVID-19, monoclonal antibodies, casirivimab, imdevimab, treatment
{"title":"First experience of using casirivimab/imdevimab in COVID-19 in the Russian Federation","authors":"P. Bogomolov, A. O. Bueverov, E. Bueverova, A.A. Кhvan, I. Maev, M.V. Arapova, N.A. Shub, E. A. Isaeva, S. V. Koblov","doi":"10.20953/1729-9225-2022-3-129-132","DOIUrl":"https://doi.org/10.20953/1729-9225-2022-3-129-132","url":null,"abstract":"The lack of effective etiotropic therapy is a serious challenge in the treatment of patients with COVID-19. The recent emergence of a new class of medications neutralizing monoclonal antibodies against the SARS-CoV-2 spike protein allows to partially solve this problem. This article presents a clinical case of a patient with an increased risk of COVID-19 complications (paroxysmal atrial fibrillation, atherogenic dyslipidemia, impaired carbohydrate tolerance) who was treated with 600 mg casirivimab and 600 mg imdevimab by intravenous infusion. A significant improvement in the patient's well-being was noted within the first 24 hours: normalization of body temperature, stool, reduction of weakness, disappearance of arthralgia and myalgia. After 48 hours, a negative test result for SARS-CoV-2 RNA was obtained, which altogether made it possible to state the recovery. There were no adverse events during and after therapy. The casirivimab and imdevimab monoclonal antibody combination may be considered as a promising etiotropic treatment for COVID-19. Key words: COVID-19, monoclonal antibodies, casirivimab, imdevimab, treatment","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67727935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.20953/1729-9225-2022-3-67-70
D. Verbenko, D. Deryabin, V. Solomka, A. Karamova, O. Obraztsova, A. Kubanov
We analyzed the sequence of the gene encoding 16S ribosomal RNA in 2 samples containing a mixture of human DNA and Mycobacterium leprae DNA obtained from two patients from the Russian Federation. We found that our sequence matched the sequence of the reference strain deposited at the National Center for Biotechnology Information (NCBI, USA). The analysis was performed using Sanger sequencing with a mixture of microbial and human DNA isolated from skin biopsy specimens. We assume that the difficulties associated with sequencing of the full-size rrs gene can be addressed by using a speciesspecific sequence of the rrs promoter region to identify M. leprae. Key words: leprosy, Mycobacterium leprae, rrs, 16S rRNA
{"title":"Taxonomic identification of Mycobacterium leprae strains isolated in the Russian Federation by assessing the sequence of the gene encoding 16S ribosomal RNA","authors":"D. Verbenko, D. Deryabin, V. Solomka, A. Karamova, O. Obraztsova, A. Kubanov","doi":"10.20953/1729-9225-2022-3-67-70","DOIUrl":"https://doi.org/10.20953/1729-9225-2022-3-67-70","url":null,"abstract":"We analyzed the sequence of the gene encoding 16S ribosomal RNA in 2 samples containing a mixture of human DNA and Mycobacterium leprae DNA obtained from two patients from the Russian Federation. We found that our sequence matched the sequence of the reference strain deposited at the National Center for Biotechnology Information (NCBI, USA). The analysis was performed using Sanger sequencing with a mixture of microbial and human DNA isolated from skin biopsy specimens. We assume that the difficulties associated with sequencing of the full-size rrs gene can be addressed by using a speciesspecific sequence of the rrs promoter region to identify M. leprae. Key words: leprosy, Mycobacterium leprae, rrs, 16S rRNA","PeriodicalId":37794,"journal":{"name":"Infektsionnye Bolezni","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67728476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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