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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.
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COVID-19 , SARS-CoV-2 , Humanos , Unidades de Cuidados Intensivos , Filogenia , Manejo de EspecímenesRESUMEN
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.
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Quirópteros/virología , Brotes de Enfermedades/prevención & control , Reservorios de Enfermedades , Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/epidemiología , Animales , Guinea/epidemiología , Fiebre Hemorrágica Ebola/transmisión , Humanos , Liberia/epidemiología , ZoonosisRESUMEN
Karachay-Cherkessia is the region in the Russian Federation that has been overlooked in terms of research on the human bacterial pathogens transmitted by ticks. In this study, we investigated the infection status of ticks with Rickettsia, Borrelia, Coxiella burmetii, Anaplasma phagocytophilum, and Ehrlichia chaffeensis/Ehrlichia muris associated with natural focal infections in Karachay-Cherkessia. A total amount of 159 ticks from three species across three genera (Ixodes ricinus, Dermacentor marginatus, Hyalomma scupense) removed from humans were collected for analysis. Additionally, we used 53 individual ticks and 40 tick pools from the vegetation of three species (I. ricinus, D. marginatus, and Rhipicephalus bursa). Screening of the studied pathogens was performed by using commercial qPCR kits. Sanger sequencing utilizing partial sequences of gltA and ompA genes was employed to identify the Rickettsia species. Our findings revealed the presence of DNA from five species within the spotted fever group Rickettsia, namely Rickettsia raoultii, R. slovaca, R. helvetica, R. monacensis, and R. aeschlimannii. Moreover, two distinct genotypes were identified within R. aeschlimannii, R. helvetica, and R. monacensis. Additionally, DNA from Borrelia burgdoferi s.l., B. miyamotoi, and A. phagocytophilum was detected in the tested ticks. This study provides valuable insights into the prevalence and the diversity of bacterial pathogens transmitted by ticks in the Karachay-Cherkessia region.
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Background: To combat the hesitancy towards implementing a hepatitis A universal mass vaccination (UMV) strategy and to provide healthcare authorities with a comprehensive analysis of the potential outcomes and benefits of the implementation of such a vaccination program, we projected HAV seroprevalence and incidence rates in the total population of the Russian Federation and estimated the pediatric vaccination threshold required to achieve an incidence level of less than 1 case per 100,000 using a new mathematical model. Methods: A dynamic age-structured SEIRV (susceptible-exposed-infectious-recovered-vaccinated) compartmental model was developed and calibrated using demographic, seroprevalence, vaccination, and epidemiological data from different regions of the Russian Federation. This model was used to project various epidemiological measures. Results: The projected national average age at the midpoint of population immunity increases from 40 years old in 2020 to 50 years old in 2036 and is shifted even further to the age of 70 years in some regions of the country. An increase of varying magnitude in the incidence of symptomatic HAV infections is predicted for all study regions and for the Russian Federation as a whole between 2028 and 2032, if the HAV vaccination coverage level remains at the level of 2022. The national average vaccination coverage level required to achieve a symptomatic HAV incidence rate below 1 case per 100,000 by 2032 was calculated to be 69.8% if children aged 1-6 years are vaccinated following the implementation of a UMV program or 34.8% if immunization is expanded to children aged 1-17 years. Conclusion: The developed model provides insights into a further decline of herd immunity to HAV against the background of ongoing viral transmission. The current favorable situation regarding hepatitis A morbidity is projected to be replaced by an increase in incidence rates if vaccination coverage remains at the current levels. The obtained results support the introduction of a hepatitis A UMV strategy in the Russian Federation.
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Vacunas contra la Hepatitis A , Hepatitis A , Humanos , Hepatitis A/epidemiología , Hepatitis A/prevención & control , Federación de Rusia/epidemiología , Niño , Incidencia , Preescolar , Vacunas contra la Hepatitis A/administración & dosificación , Adolescente , Adulto , Persona de Mediana Edad , Lactante , Estudios Seroepidemiológicos , Anciano , Masculino , Femenino , Adulto Joven , Vacunación Masiva/estadística & datos numéricos , Modelos Teóricos , Vacunación/estadística & datos numéricosRESUMEN
The indigenous populations of the Arctic regions of Russia experience the lowest coverage of health-related services. We assessed the prevalence of hepatitis A, B, C, D and E viruses (HAV, HBV, HCV, HDV and HEV) among 367 healthy adult Native people of the Arctic zone of Yakutia. The HAV seroprevalence was above and increased with age. The anti-HEV IgM and IgG antibody detection rates were 4.1% and 2.5%, respectively. The average HBsAg detection rate was 4.6%, with no positive cases identified in participants aged under 30 years, confirming the effectiveness of the newborn vaccination program that began in 1998. Anti-HDV antibodies were detected in 29.4% of HBsAg-positive cases. The anti-HCV and HCV RNA detection rates peaked in the age cohort of 50-59 years (10.8% and 3.9%). No statistically significant gender differences in the prevalence of different viral hepatitis were observed. The time-scaled phylogenetic analysis demonstrated that all HBV genotype A and D strains isolated in this study were autochthonous and had an estimated most common recent ancestor (MCRA) age of around the 11th to 14th century. Unlike HBV, the HCV strains of subtypes 1b, 2a and 2k/1b were introduced from other regions of Russia in the 1980s and 1990s. The HCV 1b sequence analysis revealed a series of transmission events. In conclusion, these data emphasize the urgent need for expanded viral hepatitis screening and care programs in the indigenous populations of the Arctic zone of Yakutia.
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Introduction: Cervical cancer (CC) is a prevalent malignancy affecting women globally. The primary causative factor of CC is the high-risk oncogenic human papillomavirus (HR-HPV). However, it is noteworthy that not all women infected with HR-HPV develop cancer, indicating the potential involvement of genetic predisposition in the development of CC. This study aims to identify genetic risks and their distribution in groups of women with different epidemiological features of HR-HPV. Materials and methods: A comparison was conducted among four groups of women, comprising 218 HPV-negative women, 120 HPV-positive women, 191 women diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or 3, and 124 women diagnosed with CC. The analysis focused on four single nucleotide polymorphisms (SNPs): rs55986091 in HLA-DQB1, rs138446575 in TTC34, rs1048943 in CYP1A1, and rs2910164 in miRNA-146a. Results: The rs55986091-A allele exhibited a protective effect within the "CC" group when compared to the "HPV-Negative" group (OR = 0.4, 95% CI= 0.25-0.65) using a log-additive model. Additionally, similar protective effects were observed in the "CIN 2/3" group compared to the "HPV-Negative" group (OR = 0.47, 95% CI = 0.28-0.79). Conclusion: The data obtained emphasize the importance of developing PCR-based diagnostic kits for the identification of SNP alleles, particularly for rs55986091, among HR-HPV-positive women within the Russian population.
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The prevalence of the tick-borne spotted fever group rickettsioses pathogens in ticks collected in Barnaul, the administrative center of Altai Krai, Western Siberia, was studied. The causative agent of tick-borne lymphadenopathy (TIBOLA) Rickettsia raoultii was revealed to be present in 61.9% of the samples from Dermacentor ticks. Moreover, Rickettsia helvetica has been identified in 5.1% of Ixodes ticks.
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A new filovirus named Menglà virus was found in bats in southern China in 2015. This species has been assigned to the new genus Dianlovirus and has only been detected in China. In this article, we report the detection of filoviruses in bats captured in Vietnam. We studied 248 bats of 15 species caught in the provinces of Lai Chau and Son La in northern Vietnam and in the province of Dong Thap in the southern part of the country. Filovirus RNA was found in four Rousettus leschenaultii and one Rousettus amplexicaudatus from Lai Chau Province. Phylogenetic analysis of the polymerase gene fragment showed that three positive samples belong to Dianlovirus, and two samples form a separate clade closer to Orthomarburgvirus. An enzyme-linked immunosorbent assay showed that 9% of Rousettus, 13% of Eonycteris, and 10% of Cynopterus bats had antibodies to the glycoprotein of marburgviruses.
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Quirópteros , Filoviridae , Marburgvirus , Animales , Vietnam/epidemiología , FilogeniaRESUMEN
BACKGROUND: Klebsiella pneumoniae, which is frequently associated with hospital- and community-acquired infections, contains multidrug-resistant (MDR), hypervirulent (hv), non-MDR/non-hv as well as convergent representatives. It is known that mostly international high-risk clonal lineages including sequence types (ST) 11, 147, 258, and 307 drive their global spread. ST395, which was first reported in the context of a carbapenemase-associated outbreak in France in 2010, is a less well-characterized, yet emerging clonal lineage. METHODS: We computationally analyzed a large collection of K. pneumoniae ST395 genomes (n = 297) both sequenced in this study and reported previously. By applying multiple bioinformatics tools, we investigated the core-genome phylogeny and evolution of ST395 as well as distribution of accessory genome elements associated with antibiotic resistance and virulence features. RESULTS: Clustering of the core-SNP alignment revealed four major clades with eight smaller subclades. The subclades likely evolved through large chromosomal recombination, which involved different K. pneumoniae donors and affected, inter alia, capsule and lipopolysaccharide antigen biosynthesis regions. Most genomes contained acquired resistance genes to extended-spectrum cephalosporins, carbapenems, and other antibiotic classes carried by multiple plasmid types, and many were positive for hypervirulence markers, including the siderophore aerobactin. The detection of "hybrid" resistance and virulence plasmids suggests the occurrence of the convergent ST395 pathotype. CONCLUSIONS: To the best of our knowledge, this is the first study that investigated a large international collection of K. pneumoniae ST395 genomes and elucidated phylogenetics and detailed genomic characteristics of this emerging high-risk clonal lineage.
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Farmacorresistencia Bacteriana , Genes Bacterianos , Klebsiella pneumoniae , beta-Lactamasas , Humanos , Antibacterianos , beta-Lactamasas/genética , Carbapenémicos , Genómica , Klebsiella pneumoniae/genética , Plásmidos , Células Clonales , Farmacorresistencia Bacteriana/genéticaRESUMEN
We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial phase I/II of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in volunteers aged 18-60 and open multi-center comparative phase IIb clinical trial in volunteers aged 60 years and older. The safety of the vaccine was assessed in 400 volunteers in the 18-60 age cohort who received two doses of the vaccine (n = 300) or placebo (n = 100) and in 200 volunteers in 60+ age cohort all of whom received three doses of the vaccine. The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AEs), or other significant AEs related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p < 0.05). Immunogenicity assessment in stage 3 of Phase II was performed on 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening. On Day 42 after the 1st vaccination, the seroconversion rate in participants who were seronegative at screening was 86.9%, with the average geometric mean neutralizing antibody (nAB) titer of 1:20. A statistically significant (p < 0.05) increase in IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the 1st vaccination. In participants who were seropositive at screening but had nAB titers below 1:256, the rate of fourfold increase in nAB levels was 85.2%, while in the participants with nAB titers > 1:256, the rate of fourfold increase in nAB levels was below 45%; the participants who were seropositive at screening of the 2nd vaccination did not lead to a significant increase in nAB titers. In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with over 85% NT seroconversion rates after complete vaccination course in participants who were seronegative at screening in both age groups: 18-60 and 60+. In participants who were seropositive at screening and had nAB titers below 1:256, a single vaccination led to a fourfold increase in nAB levels in 85.2% of cases. These findings indicate that CoviVac can be successfully used both for primary vaccination in a two-dose regimen and for booster vaccination as a single dose in individuals with reduced neutralizing antibody levels.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Persona de Mediana Edad , Anciano , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Vacunas Atenuadas , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
BACKGROUND: According to the World Health Organization, more than 250 million people worldwide are chronically infected with the hepatitis B virus, and almost 800.000 patients die annually of mediated liver disorders. Therefore, adequate biological test systems are needed that could fully simulate the course of chronic hepatitis B virus infection, including in patients with hepatocellular carcinoma. METHODS: In this study, we will assess the effectiveness of existing protocols for isolation and cultivation of primary cells derived from patients with hepatocellular carcinoma in terms of the yield of viable cells and their ability to replicate the hepatitis B virus using isolation and cultivation methods for adhesive primary cells, flow cytometry and quantitative polymerase chain reaction. Another part of our study will be devoted to evaluating the effectiveness of hepatocellular carcinoma grafting methods to obtain patient-derived heterotopic and orthotopic xenograft mouse avatars using animal X-ray irradiation and surgery procedures and in vivo fluorescent signals visualization and measurements. Our study will be completed by histological methods. DISCUSSION: This will be the first extensive comparative study of the main modern methods and protocols for isolation and cultivation primary hepatocellular carcinoma cells and tumor engraftment to the mice. All protocols will be optimized and characterized using the: (1) efficiency of the method for isolation cells from removed hepatocellular carcinoma in terms of their quantity and viability; (2) efficiency of the primary cell cultivation protocol in terms of the rate of monolayer formation and hepatitis B virus replication; (3) efficiency of the grafting method in terms of the growth rate and the possibility of hepatitis B virus persistence and replication in mice. The most effective methods will be recommended for use in translational biomedical research.
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Modelos Animales de Enfermedad , Hepatitis C Crónica/patología , Cultivo Primario de Células/métodos , Ensayos Antitumor por Modelo de Xenoinjerto/normas , Animales , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Células Cultivadas , Hepatitis C Crónica/virología , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Delta has outcompeted most preexisting variants of SARS-CoV-2, becoming the globally predominant lineage by mid-2021. Its subsequent evolution has led to the emergence of multiple sublineages, most of which are well-mixed between countries. By contrast, here we show that nearly the entire Delta epidemic in Russia has probably descended from a single import event, or from multiple closely timed imports from a single poorly sampled geographic location. Indeed, over 90 per cent of Delta samples in Russia are characterized by the nsp2:K81N + ORF7a:P45L pair of mutations which is rare outside Russia, putting them in the AY.122 sublineage. The AY.122 lineage was frequent in Russia among Delta samples from the start, and has not increased in frequency in other countries where it has been observed, suggesting that its high prevalence in Russia has probably resulted from a random founder effect rather than a transmission advantage. The apartness of the genetic composition of the Delta epidemic in Russia makes Russia somewhat unusual, although not exceptional, among other countries.
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BACKGROUND: Delivery of CRISPR/Cas RNPs to target cells still remains the biggest bottleneck to genome editing. Many efforts are made to develop efficient CRISPR/Cas RNP delivery methods that will not affect viability of target cell dramatically. Popular current methods and protocols of CRISPR/Cas RNP delivery include lipofection and electroporation, transduction by osmocytosis and reversible permeabilization and erythrocyte-based methods. METHODS: In this study we will assess the efficiency and optimize current CRISPR/Cas RNP delivery protocols to target cells. We will conduct our work using molecular cloning, protein expression and purification, cell culture, flow cytometry (immunocytochemistry) and cellular imaging techniques. DISCUSSION: This will be the first extensive comparative study of popular current methods and protocols of CRISPR/Cas RNP delivery to human cell lines and primary cells. All protocols will be optimized and characterized using the following criteria i) protein delivery and genome editing efficacy; ii) viability of target cells after delivery (post-transduction recovery); iii) scalability of delivery process; iv) cost-effectiveness of the delivery process and v) intellectual property rights. Some methods will be considered 'research-use only', others will be recommended for scaling and application in the development of cell-based therapies.
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Clonación Molecular/métodos , Edición Génica/métodos , Ribonucleoproteínas/metabolismo , Sistemas CRISPR-Cas/genética , Técnicas de Cultivo de Célula , Línea Celular , Tratamiento Basado en Trasplante de Células y Tejidos , Análisis Costo-Beneficio , Electroporación , Técnicas de Transferencia de Gen/instrumentación , Técnicas de Transferencia de Gen/tendencias , Humanos , ARN Guía de Kinetoplastida/genética , Ribonucleoproteínas/genéticaRESUMEN
Polymyxin resistance, determined by mcr genes located on plasmid DNA, currently poses a high epidemiological threat. Non-typhoid Salmonella (NTS) are one of the key pathogens causing diarrheal diseases. Here, we report the isolation and whole genome sequencing of multidrug colistin-resistant/susceptible isolates of non-typhoid Salmonella enterica serovars carrying mcr genes. Non-typhoid strains of Salmonella enterica subsp. enterica were isolated during microbiological monitoring of the environment, food, and diarrheal disease patients between 2018 and 2020 in Russia (n = 586). mcr-1 genes were detected using a previously developed qPCR assay, and whole genome sequencing of mcr positive isolates was performed by both short-read (Illumina) and long-read (Oxford Nanopore) approaches. Three colistin-resistant isolates, including two isolates of S. Enteritidis and one isolate of S. Bovismorbificans, carried the mcr-1.1 gene located on IncX4 and IncI2 conjugative plasmids, respectively. The phenotypically colistin-susceptible isolate of S. Typhimurium carried a mcr-9 gene on plasmid IncHI2. In conclusion, we present the first three cases of mcr gene-carrying NTS isolates detected in Russia with both outbreak and sporadic epidemiological backgrounds.
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BACKGROUND: Delta has outcompeted most preexisting variants of SARS-CoV-2, becoming the globally predominant lineage by mid-2021. Its subsequent evolution has led to emergence of multiple sublineages, many of which are well-mixed between countries. AIM: Here, we aim to study the emergence and spread of the Delta lineage in Russia. METHODS: We use a phylogeographic approach to infer imports of Delta sublineages into Russia, and phylodynamic models to assess the rate of their spread. RESULTS: We show that nearly the entire Delta epidemic in Russia has probably descended from a single import event despite genetic evidence of multiple Delta imports. Indeed, over 90% of Delta samples in Russia are characterized by the nsp2:K81N+ORF7a:P45L pair of mutations which is rare outside Russia, putting them in the AY.122 sublineage. The AY.122 lineage was frequent in Russia among Delta samples from the start, and has not increased in frequency in other countries where it has been observed, suggesting that its high prevalence in Russia has probably resulted from a random founder effect. CONCLUSION: The apartness of the genetic composition of the Delta epidemic in Russia makes Russia somewhat unusual, although not exceptional, among other countries.