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BACKGROUND: The Covid-19 pandemic has been characterized by the emergence of novel SARS-CoV-2 variants, each with distinct properties influencing transmission dynamics, immune escape, and virulence, which, in turn, influence their impact on local populations. Swift analysis of the properties of newly emerged variants is essential in the initial days and weeks to enhance readiness and facilitate the scaling of clinical and public health system responses. METHODS: This paper introduces a two-variant metapopulation compartmental model of disease transmission to simulate the dynamics of disease transmission during a period of transition to a newly dominant strain. Leveraging novel S-gene dropout analysis data and genomic sequencing data, combined with confirmed Covid-19 case data, we estimate the epidemiological characteristics of the Omicron variant, which replaced the Delta variant in late 2021 in Philadelphia, PA. We utilized a grid-search method to identify plausible combinations of model parameters, followed by an ensemble adjustment Kalman filter for parameter inference. RESULTS: The model successfully estimated key epidemiological parameters; we estimated the ascertainment rate of 0.22 (95% credible interval 0.15-0.29) and transmission rate of 5.0 (95% CI 2.4-6.6) for the Omicron variant. CONCLUSIONS: The study demonstrates the potential for this model-inference framework to provide real-time insights during the emergence of novel variants, aiding in timely public health responses.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/transmisión , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Philadelphia/epidemiologíaRESUMEN
Seasonal influenza A virus subtype H3N2 (A/H3N2) circulates globally and has been linked to higher hospitalization rates and summer outbreaks in temperate regions. Here, A/H3N2 circulation in Shanghai, China was systematically studied using data and materials generated by the Shanghai influenza surveillance network from 2005 to 2023. Time-series analysis of incidence and subtyping data showed that A/H3N2 co-circulated with other (sub)types and dominated in multiple seasonal influenza peaks, preferentially in summer. Whole genomes of 528 representative strains were sequenced, and spatiotemporal phylodynamic analysis using these and GISAID-archived sequences demonstrated that in the years before the COVID-19 pandemic, phylogenetically similar strains were circulating locally and elsewhere. However, clade 1a.1 (within 3C.2a.1b.2a), circulated in and only in Shanghai and domestically in 2022, while the sibling clade 2 predominated in other regions. Interestingly, clade 1a.1 was swiftly and completely replaced by clade 2, mostly 2a.3a.1, at the start of 2023. In hemagglutination inhibition and neutralization assays, sera from healthy donors collected in 2022 displayed higher or similar reactivity against 2a.3a.1 compared to 1a.1. By contrast, transcription and replication competence of 2a.3a.1 in MDCK cells was higher than 1a.1. These results indicated that instead of antigenicity differences enabling evasion of pre-existing immunity, higher replicative capability more likely contributed to 2a.3a.1 viruses achieving dominance in China. In addition to summarizing patterns of A/H3N2 local circulation in Shanghai, this work revealed an unusual episode in A/H3N2 global circulation and evolution dynamics in connection to the COVID-19 pandemic and explored possible mechanistic explanations.
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Genoma Viral , Subtipo H3N2 del Virus de la Influenza A , Gripe Humana , Filogenia , Secuenciación Completa del Genoma , China/epidemiología , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/clasificación , Humanos , Gripe Humana/virología , Gripe Humana/epidemiología , COVID-19/epidemiología , COVID-19/virología , Estaciones del Año , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/inmunología , Células de Riñón Canino Madin Darby , Perros , AnimalesRESUMEN
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new emerging coronavirus that caused coronavirus disease 2019 (COVID-19). Whole-genome tracking of SARS-CoV-2 enhanced our understanding of the mechanism of the disease, control, and prevention of COVID-19. METHODS: we analyzed 3368 SARS-CoV-2 protein sequences from Iran and compared them with 15.6 million global sequences in the GISAID database, using the Wuhan-Hu-1 strain as a reference. RESULTS: Our investigation revealed that NSP12-P323L, ORF9c-G50N, NSP14-I42V, membrane-A63T, Q19E, and NSP3-G489S were found to be the most frequent mutations among Iranian SARS-CoV-2 sequences. Furthermore, it was observed that more than 94% of the SARS-CoV-2 genome, including NSP7, NSP8, NSP9, NSP10, NSP11, and ORF8, had no mutations when compared to the Wuhan-Hu-1 strain. Finally, our data indicated that the ORF3a-T24I, NSP3-G489S, NSP5-P132H, NSP14-I42V, envelope-T9I, nucleocapsid-D3L, membrane-Q19E, and membrane-A63T mutations might be responsible factors for the surge in the SARS-CoV-2 Omicron variant wave in Iran. CONCLUSIONS: real-time genomic surveillance is crucial for detecting new SARS-CoV-2 variants, updating diagnostic tools, designing vaccines, and understanding adaptation to new environments.
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COVID-19 , Genoma Viral , Mutación , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Irán/epidemiología , Humanos , COVID-19/virología , COVID-19/epidemiología , Sustitución de Aminoácidos , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
BACKGROUND: The COVID-19 pandemic has underscored the critical role of sequencing technology in disease control and outbreak response. However, resource limitations and challenging environments often impede such efforts in low and middle-income countries. This study aimed to investigate the spectrum of viral co-infections, particularly with human viral pathogens, in SARS-CoV-2 positive individuals in Sierra Leone using metagenomic sequencing, evaluating the feasibility of utilizing this technology for epidemiological and evolutionary surveillance of pathogens related to public health in low-income environments. METHODS: We retrospectively collected and analyzed 98 nasopharyngeal swab specimens from SARS-CoV-2 positive individuals in Sierra Leone. Samples were pre-processed locally and transferred to China via FTA cards for metagenomic sequencing, which was performed using the Novaseq platform. The study focused on the identification of nasopharyngeal viruses co-infecting with SARS-CoV-2, with a deeper analysis of significant human viral pathogens such as HPV. RESULTS: The study identified 22 viral taxa from 20 families, including 4 human viruses. Notably, 19.4% of samples showed HPV co-infection with 34 distinct types, predominantly beta and gamma HPVs. Multiple HPV types were found in individual samples, indicating a high complexity of viral co-infections. CONCLUSIONS: The identification of a wide range of co-infecting viruses, particularly multiple HPV genotypes, highlights the complexity of viral interactions and their potential implications for public health. These findings enhance our understanding of viral co-infections and provide valuable insights for public health interventions in Sierra Leone. Further research is needed to explore the clinical significance of these findings and their impact on disease outcomes.
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COVID-19 , Coinfección , Infecciones por Papillomavirus , SARS-CoV-2 , Humanos , Sierra Leona/epidemiología , Estudios Retrospectivos , COVID-19/virología , COVID-19/epidemiología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/clasificación , Coinfección/virología , Coinfección/epidemiología , Femenino , Adulto , Masculino , Persona de Mediana Edad , Adulto Joven , Nasofaringe/virología , Adolescente , Metagenómica , Filogenia , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Anciano , NiñoRESUMEN
Human enteroviruses are highly prevalent world-wide. Up to more than 100 subtypes of enteroviruses can cause several diseases, including encephalitis, meningitis, myocarditis, hand-foot-mouth disease, conjunctivitis, respiratory diseases, and gastrointestinal diseases, thus posing a great threat to human health. This study aimed to investigate the epidemiological characteristics of enterovirus in children in Hangzhou, China before and after the COVID-19 outbreak. Systematic monitoring of enterovirus infections was performed by collecting samples from the children admitted to the inpatient wards and outpatient departments in the Children's Hospital, Zhejiang University School of Medicine, between January 2019 and May 2023. A commercial real-time RT PCR kit was utilized to detect enteroviruses. Among the 34,152 samples collected, 1162 samples, accounting for 3.4% of the samples, were tested positive for enteroviruses. The annual positive rates of the enteroviruses were 5.46%, 1.15%, 4.43%, 1.62%, and 1.96% in 2019, 2020, 2021, 2022, and May 2023, respectively. The positivity rate of the enteroviruses was highest among children aged 3-5 years and 5-7 years. Moreover, the monthly positivity rate of enterovirus infection ranged from 0.32% to 10.38%, with a peak in June and July. Serotypes, especially EV71 and CA16, causing severe symptoms such as HFMD, were decreasing, while the proportion of unidentified serotypes was on the rise. The incidence of enteroviruses in Hangzhou was higher in children aged 1-3 years and 7-18 years.
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Infecciones por Enterovirus , Enterovirus , Humanos , China/epidemiología , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/virología , Niño , Preescolar , Lactante , Masculino , Enterovirus/clasificación , Enterovirus/genética , Enterovirus/aislamiento & purificación , Femenino , Adolescente , COVID-19/epidemiología , COVID-19/virología , Recién Nacido , Estaciones del Año , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , PrevalenciaRESUMEN
Sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes throughout the COVID-19 pandemic has generated a wealth of data on viral evolution across populations, but only a few studies have so far explored SARS-CoV-2 evolution across large connected transmission networks. Here, we couple data from SARS-CoV-2 sequencing with contact tracing data from an outbreak with a single origin in a rural Norwegian community where samples from all exposed persons were collected prospectively. A total of 134 nasopharyngeal samples were positive by PCR. Among the 121 retrievable genomes, 81 were identical to the genome of the introductor, thus demonstrating that genomics beyond clustering genotypically similar viral genomes to confirm relatedness offers limited additional value to manual contact tracing. In the cases where mutations were discovered, five small genetic clusters were identified. We observed a household secondary attack rate of 77%, with 92% of household members infected among households with secondary transmission, suggesting that SARS-CoV-2 introduction into large families is likely to affect all household members. IMPORTANCE: In outbreak investigations, obtaining a full overview of infected individuals within a population is seldom achieved. We here present an example where a single introduction of B1.1.7 SARS-CoV-2 within a rural community allowed for tracing of the virus from an introductor via dissemination through larger gatherings into households. The outbreak occurred before widespread vaccination, allowing for a "natural" outbreak development with community lockdown. We show through sequencing that the virus can infect up to five consecutive persons without gaining mutations, thereby showing that contact tracing seems more important than sequencing for local outbreak investigations in settings with few alternative introductory transmission pathways. We also show how larger households where a child introduced transmission appeared more likely to promote further spread of the virus compared to households with an adult as the primary introductor.
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COVID-19 , Trazado de Contacto , Brotes de Enfermedades , Composición Familiar , Genoma Viral , Población Rural , SARS-CoV-2 , Humanos , COVID-19/transmisión , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Adulto , Femenino , Persona de Mediana Edad , Masculino , Noruega/epidemiología , Anciano , Niño , Adolescente , Adulto Joven , Preescolar , Lactante , Variación Genética , Mutación , Anciano de 80 o más AñosRESUMEN
As demonstrated by the SARS-CoV-2 pandemic, the emergence of novel viral strains with increased transmission rates poses a serious threat to global health. Statistical models of genome sequence evolution may provide a critical tool for early detection of these strains. Using a novel stochastic model that links transmission rates to the entire viral genome sequence, we study the utility of phylogenetic methods that use a phylogenetic tree relating viral samples versus count-based methods that use case counts of variants over time exclusively to detect increased transmission rates and identify candidate causative mutations. We find that phylogenies in particular can detect novel transmission-enhancing variants very soon after their origin and may facilitate the development of early detection systems for outbreak surveillance.
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COVID-19 , Genoma Viral , Filogenia , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , Humanos , COVID-19/virología , COVID-19/transmisión , COVID-19/epidemiología , Mutación , Genómica/métodos , Evolución MolecularRESUMEN
Several coronaviruses infect humans, with three, including the SARS-CoV2, causing diseases. While coronaviruses are especially prone to induce pandemics, we know little about their evolutionary history, host-to-host transmissions, and biogeography. One of the difficulties lies in dating the origination of the family, a particularly challenging task for RNA viruses in general. Previous cophylogenetic tests of virus-host associations, including in the Coronaviridae family, have suggested a virus-host codiversification history stretching many millions of years. Here, we establish a framework for robustly testing scenarios of ancient origination and codiversification versus recent origination and diversification by host switches. Applied to coronaviruses and their mammalian hosts, our results support a scenario of recent origination of coronaviruses in bats and diversification by host switches, with preferential host switches within mammalian orders. Hotspots of coronavirus diversity, concentrated in East Asia and Europe, are consistent with this scenario of relatively recent origination and localized host switches. Spillovers from bats to other species are rare, but have the highest probability to be towards humans than to any other mammal species, implicating humans as the evolutionary intermediate host. The high host-switching rates within orders, as well as between humans, domesticated mammals, and non-flying wild mammals, indicates the potential for rapid additional spreading of coronaviruses across the world. Our results suggest that the evolutionary history of extant mammalian coronaviruses is recent, and that cases of long-term virus-host codiversification have been largely over-estimated.
The SARS-CoV-2 virus, which caused the recent global coronavirus pandemic, is the latest in a string of coronaviruses that have caused serious outbreaks. This group of coronaviruses can also infect other mammals and likely jumped between species including from non-humans to humans over the course of evolution. Determining when and how viruses evolved to infect humans can help scientists predict and prevent outbreaks. However, tracking the evolutionary trajectory of coronaviruses is challenging, and there are conflicting views on how often coronaviruses crossed between species and when these transitions likely occurred. Some studies suggest that coronaviruses originated early on in evolution and evolved together with their mammalian hosts, only occasionally jumping to and from different species. While others suggest they appeared more recently, and rapidly diversified by regularly transferring between species. To determine which is the most likely scenario, Maestri, Perez-Lamarque et al. developed a computational approach using already available data on the genetics and evolutionary history of mammals and coronaviruses. This revealed that coronaviruses originated recently in bats from East Asia and Europe, and primarily evolved by rapidly transferring between different mammalian species. This has led to geographical hotspots of diverse coronaviruses in East Asia and Europe. Maestri, Perez-Lamarque et al. found that it was rare for coronaviruses to spill over from bats to other types of mammals. Most of these spillovers resulted from coronaviruses jumping from bats to humans or domesticated animals. Humans appeared to be the main intermediary host that coronaviruses temporarily infected as they transferred from bats to other mammals. These findings that coronaviruses emerged recently in evolution, jumped relatively frequently between species, and are geographically restricted suggest that future transmissions are likely. Gathering more coronavirus samples from across the world and using even more powerful analysis tools could help scientists understand more about how these viruses recently evolved. These insights may lead to strategies for preventing new coronaviruses from emerging and spreading among humans.
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Quirópteros , Coronavirus , Mamíferos , Animales , Mamíferos/virología , Quirópteros/virología , Coronavirus/genética , Coronavirus/clasificación , Humanos , Filogenia , Evolución Molecular , Especificidad del Huésped , Europa (Continente) , Variación Genética , Evolución Biológica , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/fisiologíaRESUMEN
The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants constitute a challenge for public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 in California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages.
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COVID-19 , Genoma Viral , Filogenia , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/clasificación , COVID-19/virología , COVID-19/epidemiología , California/epidemiología , Humanos , Recombinación GenéticaRESUMEN
The first case of COVID-19 was detected in Bangladesh on 8 March 2020. Since then, the Government of Bangladesh (GoB) has implemented various measures to limit the transmission of COVID-19, including widespread testing facilities across the nation through a laboratory network for COVID-19 molecular testing. This study aimed to analyze the dynamics of SARS-CoV-2 in Bangladesh by conducting COVID-19 testing and genomic surveillance of the virus variants throughout the pandemic. Nasopharyngeal swabs were collected from authorized GoB collection centers between April 2020 and June 2023. The viral RNA was extracted and subjected to real-time PCR analysis in icddr,b's Virology laboratory. A subset of positive samples underwent whole-genome sequencing to track the evolutionary footprint of SARS-CoV-2 variants. We tested 149,270 suspected COVID-19 cases from Dhaka (n = 81,782) and other districts (n = 67,488). Of these, 63% were male. The highest positivity rate, 27%, was found in the >60 years age group, followed by 26%, 51-60 years, 25% in 41-50 years, and the lowest, 9% in under five children. Notably, the sequencing of 2742 SARS-CoV-2 genomes displayed a pattern of globally circulating variants, Alpha, Beta, Delta, and Omicron, successively replacing each other over time and causing peaks of COVID-19 infection. Regarding the risk of SARS-CoV-2 infection, it was observed that the positivity rate increased with age compared to the under-5 age group in 2020 and 2021. However, these trends did not remain consistent in 2022, where older age groups, particularly those over 60, had a lower positivity rate compared to other age groups due to vaccination. The study findings generated data on the real-time circulation of different SARS-CoV-2 variants and the upsurge of COVID-19 cases in Bangladesh, which impacted identifying hotspots and restricting the virus from further transmission. Even though there is currently a low circulation of SARS-CoV-2 in Bangladesh, similar approaches of genomic surveillance remain essential for monitoring the emergence of new SARS-CoV-2 variants or other potential pathogens that could lead to future pandemics.
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COVID-19 , Genoma Viral , SARS-CoV-2 , Bangladesh/epidemiología , Humanos , COVID-19/epidemiología , COVID-19/virología , COVID-19/transmisión , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , Masculino , Adulto , Persona de Mediana Edad , Femenino , Adolescente , Niño , Preescolar , Adulto Joven , Lactante , Secuenciación Completa del Genoma , Anciano , Recién Nacido , Filogenia , ARN Viral/genéticaRESUMEN
Vast amounts of pathogen genomic, demographic and spatial data are transforming our understanding of SARS-CoV-2 emergence and spread. We examined the drivers of molecular evolution and spread of 291,791 SARS-CoV-2 genomes from Denmark in 2021. With a sequencing rate consistently exceeding 60%, and up to 80% of PCR-positive samples between March and November, the viral genome set is broadly whole-epidemic representative. We identify a consistent rise in viral diversity over time, with notable spikes upon the importation of novel variants (e.g., Delta and Omicron). By linking genomic data with rich individual-level demographic data from national registers, we find that individuals aged < 15 and > 75 years had a lower contribution to molecular change (i.e., branch lengths) compared to other age groups, but similar molecular evolutionary rates, suggesting a lower likelihood of introducing novel variants. Similarly, we find greater molecular change among vaccinated individuals, suggestive of immune evasion. We also observe evidence of transmission in rural areas to follow predictable diffusion processes. Conversely, urban areas are expectedly more complex due to their high mobility, emphasising the role of population structure in driving virus spread. Our analyses highlight the added value of integrating genomic data with detailed demographic and spatial information, particularly in the absence of structured infection surveys.
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COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , Dinamarca/epidemiología , COVID-19/epidemiología , COVID-19/virología , COVID-19/transmisión , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Genoma Viral/genética , Adulto , Persona de Mediana Edad , Anciano , Adolescente , Adulto Joven , Evolución Molecular , Masculino , Femenino , Preescolar , Niño , Filogenia , LactanteRESUMEN
Lumpy skin disease virus (LSDV), a double-stranded DNA virus from the Capripoxvirus genus, primarily affects Bos indicus, Bos taurus breeds, and water buffalo. Arthropod vectors, including mosquitoes and biting flies, are the main LSDV transmitters. Although LSDV is not zoonotic, this study unexpectedly detected LSDV reads in the upper respiratory tract microbiome of humans from rural and urban areas in Maharashtra, India. Nasopharyngeal and oropharyngeal swab samples collected for SARS-CoV-2 surveillance underwent whole-genome metagenomics sequencing, revealing LSDV reads in 25% of samples. Split kmer analysis provided insights into sample relatedness despite the low coverage of LSDV reads with the reference genome. Our findings, which include the detection of LSDV contigs aligning to specific locations on the reference genome, suggest a common source for LSDV reads, potentially shared water sources, or milk/milk products. Further investigation is needed to ascertain the mode of transmission and reason for the detection of LSDV reads in human upper respiratory tract.
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Virus de la Dermatosis Nodular Contagiosa , Metagenómica , Microbiota , Humanos , Microbiota/genética , Metagenómica/métodos , Virus de la Dermatosis Nodular Contagiosa/aislamiento & purificación , Virus de la Dermatosis Nodular Contagiosa/genética , Virus de la Dermatosis Nodular Contagiosa/clasificación , Orofaringe/virología , Orofaringe/microbiología , Animales , India , Genoma Viral/genética , Nasofaringe/virología , Nasofaringe/microbiología , Sistema Respiratorio/microbiología , Sistema Respiratorio/virología , Masculino , Secuenciación Completa del Genoma , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/clasificación , Femenino , Adulto , COVID-19/diagnóstico , COVID-19/virología , Dermatosis Nodular Contagiosa/virologíaRESUMEN
BACKGROUND: Currently, there is limited understanding of the specific humoral immune response in BA.5-infected hemodialysis patients (BA.5-CHDPs) with previous COVID-19 vaccination. Additionally, the relevant risk factors for reinfection with XBB variants in BA.5-CHDPs have yet to be elucidated. METHOD: A total of 178 BA.5-CHDPs were enrolled in this study among 53 patients who had previous vaccination. To compare hemodialysis patients in both unvaccinated and vaccinated for their immune response to the BA.5 subtype infection, we assessed serum levels of anti-ancestral-S1-IgG, anti-BA.5-receptor binding domain (RBD)-IgG, and anti-XBB.1.16-RBD-IgG using enzyme-linked immunosorbent assay, the neutralizing antibody titer against BA.5 and XBB.1.16 was determined using pseudovirus neutralization assays. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with severe infection, the magnitude of specific humoral immunity and susceptibility to XBB variants reinfection. RESULT: Our findings indicate that BA.5-CHDPs with full or booster vaccinations have higher levels of anti-ancestral-S1-IgG than unvaccinated individuals. However, levels of anti-BA.5-RBD-IgG and anti-XBB.1.16-RBD-IgG are much lower. Booster-vaccinated BA.5-CHDPs have significantly higher levels of BA.5 and XBB.1.16 specific antibodies and neutralizing antibodies than unvaccinated patients. Low globulin levels and shorter hemodialysis duration are independent risk factors for XBB reinfection in BA.5-CHDPs. CONCLUSION: Although XBB.1.16 specific neutralizing antibody levels were low in BA.5-CHDPs, these levels cannot predict the risk of reinfection; other potential risk factors need to be investigated in the future.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Inmunidad Humoral , Diálisis Renal , SARS-CoV-2 , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , China/epidemiología , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Reinfección/inmunología , Factores de Riesgo , SARS-CoV-2/clasificación , SARS-CoV-2/inmunología , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , VacunaciónRESUMEN
PURPOSE: In this study, we present DeepVirusClassifier, a tool capable of accurately classifying Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral sequences among other subtypes of the coronaviridae family. This classification is achieved through a deep neural network model that relies on convolutional neural networks (CNNs). Since viruses within the same family share similar genetic and structural characteristics, the classification process becomes more challenging, necessitating more robust models. With the rapid evolution of viral genomes and the increasing need for timely classification, we aimed to provide a robust and efficient tool that could increase the accuracy of viral identification and classification processes. Contribute to advancing research in viral genomics and assist in surveilling emerging viral strains. METHODS: Based on a one-dimensional deep CNN, the proposed tool is capable of training and testing on the Coronaviridae family, including SARS-CoV-2. Our model's performance was assessed using various metrics, including F1-score and AUROC. Additionally, artificial mutation tests were conducted to evaluate the model's generalization ability across sequence variations. We also used the BLAST algorithm and conducted comprehensive processing time analyses for comparison. RESULTS: DeepVirusClassifier demonstrated exceptional performance across several evaluation metrics in the training and testing phases. Indicating its robust learning capacity. Notably, during testing on more than 10,000 viral sequences, the model exhibited a more than 99% sensitivity for sequences with fewer than 2000 mutations. The tool achieves superior accuracy and significantly reduced processing times compared to the Basic Local Alignment Search Tool algorithm. Furthermore, the results appear more reliable than the work discussed in the text, indicating that the tool has great potential to revolutionize viral genomic research. CONCLUSION: DeepVirusClassifier is a powerful tool for accurately classifying viral sequences, specifically focusing on SARS-CoV-2 and other subtypes within the Coronaviridae family. The superiority of our model becomes evident through rigorous evaluation and comparison with existing methods. Introducing artificial mutations into the sequences demonstrates the tool's ability to identify variations and significantly contributes to viral classification and genomic research. As viral surveillance becomes increasingly critical, our model holds promise in aiding rapid and accurate identification of emerging viral strains.
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COVID-19 , Aprendizaje Profundo , Genoma Viral , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Genoma Viral/genética , COVID-19/virología , Coronaviridae/genética , Coronaviridae/clasificación , Humanos , Redes Neurales de la ComputaciónRESUMEN
Introduction. After two seasons of absence and low circulation, influenza activity increased significantly in the winter of 2022-2023. This study aims to characterize virological and epidemiological aspects of influenza infection in Bulgaria during the 2022-2023 season and perform a phylogenetic/molecular analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of representative influenza strains.Hypothesis/Gap Statement. Influenza A and B viruses generate new genetic groups/clades each season, replacing previously circulating variants. This results in increased antigenic distances from current vaccine strains. Strengthening existing influenza surveillance is essential to meet the challenges posed by the co-circulation of influenza and SARS-CoV-2.Methodology. We tested 2713 clinical samples from patients with acute respiratory illnesses using a multiplex real-time RT-PCR kit (FluSC2) to detect influenza A/B and Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) simultaneously. Representative Bulgarian influenza strains were sequenced at the WHO Collaborating Centres in London, UK, and Atlanta, USA.Results. Influenza virus was detected in 694 (25.6â%) patients. Of these, 364 (52.4â%), 213 (30.7â%) and 117 (16.9â%) were positive for influenza A(H1N1)pdm09, A(H3N2) and B/Victoria lineage virus, respectively. HA genes of the 47 influenza A(H1N1)pdm09 viruses fell into clades 5a.2. and 5a.2a.1 within the 6B.5A.1A.5a.2 group. Twenty-seven A(H3N2) viruses belonging to subclades 2b, 2a.1, 2a.1b and 2a.3a.1 within the 3C.2a1b.2a.2 group were analysed. All 23 sequenced B/Victoria lineage viruses were classified into the V1A.3a.2 group. We identified amino acid substitutions in HA and NA compared with the vaccine strains, including several substitutions in the HA antigenic sites.Conclusion. The study's findings showed genetic diversity among the influenza A viruses and, to a lesser extent, among B viruses, circulating in the first season after the lifting of anti-COVID-19 measures.
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Variación Genética , Virus de la Influenza B , Gripe Humana , Neuraminidasa , Filogenia , SARS-CoV-2 , Humanos , Gripe Humana/virología , Gripe Humana/epidemiología , Virus de la Influenza B/genética , Virus de la Influenza B/clasificación , Virus de la Influenza B/aislamiento & purificación , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Neuraminidasa/genética , Adulto , Masculino , Persona de Mediana Edad , Femenino , Bulgaria/epidemiología , Adulto Joven , Anciano , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Preescolar , Niño , Adolescente , COVID-19/epidemiología , COVID-19/virología , Lactante , Estaciones del Año , Virus de la Influenza A/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/aislamiento & purificación , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/clasificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificaciónRESUMEN
Enteroviruses (EVs) are ubiquitous viruses that circulate worldwide, causing sporadic or epidemic infections, typically during the summer and fall. They cause a broad spectrum of illnesses, ranging from an unspecified febrile clinical presentation to a severe illness. EVs are recognized to be the most frequent etiological agents of aseptic meningitis in children. However, as the infection is usually mild and self-limiting, it remains underestimated, and the epidemiology of EVs is poorly understood. To date, no vaccine or effective therapy for all types of enteroviruses is available, and EVs constitute a public health concern. Here, we investigated the molecular epidemiology of EV strains circulating in the Lazio region over a 10-year time span (2012-2023) by using a sequence-typing approach and phylogenetic analysis. The epidemiological trend of EV infection has undergone changes during the SARS-CoV-2 pandemic (2020-2021), which resulted in a modification in terms of the number of diagnosed cases and seasonality. From 2022, the circulation of EVs showed a behavior typical of the pre-pandemic period, although changes in predominantly circulating strains have been noted. Both epidemic and sporadic circulation events have been characterized in the Lazio region. Further analyses are needed to better characterize any strain with higher potential pathogenic power and to identify possible recombinant strains.
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Infecciones por Enterovirus , Enterovirus , Genotipo , Epidemiología Molecular , Filogenia , Humanos , Infecciones por Enterovirus/virología , Infecciones por Enterovirus/epidemiología , Enterovirus/genética , Enterovirus/clasificación , Enterovirus/aislamiento & purificación , Estaciones del Año , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , SARS-CoV-2/clasificación , NiñoRESUMEN
After the first phase of the COVID-19 pandemic in Europe, a new highly pathogenic variant of echovirus 11 (E11) was detected. The aim of this study was to analyze the genetic diversity of Polish E11 environmental and clinical strains circulating between 2017 and 2023 as well as compare them with E11 strains isolated from severe neonatal sepsis cases reported in Europe between 2022 and 2023. Additionally, the study explores the effectiveness of environmental monitoring in tracking the spread of new variants. For this purpose, the complete sequences of the VP1 capsid protein gene were determined for 266 E11 strains isolated in Poland from 2017 to 2023, and phylogenetic analysis was performed. In the years 2017-2023, a significant increase in the detection of E11 strains was observed in both environmental and clinical samples in Poland. The Polish E11 strains represented three different genotypes, C3, D5 and E, and were characterized by a high diversity. In Poland, the intensive circulation of the new variant E11, responsible for severe neonatal infections with a high mortality in Europe, was detected in the years 2022-2023. This investigation demonstrates the important role of environmental surveillance in the tracking of enteroviruses circulation, especially in settings with limited clinical surveillance.
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COVID-19 , Enterovirus Humano B , Filogenia , SARS-CoV-2 , Polonia/epidemiología , Humanos , Enterovirus Humano B/genética , Enterovirus Humano B/clasificación , Enterovirus Humano B/aislamiento & purificación , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , Genotipo , Variación Genética , Proteínas de la Cápside/genética , Recién Nacido , Infecciones por Echovirus/epidemiología , Infecciones por Echovirus/virología , PandemiasRESUMEN
SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion1 and affect other properties that contribute to viral fitness, such as ACE2 receptor binding and cell entry2,3. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning4 to measure how more than 9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully affected ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456 and 473; however, the antigenic effects of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however, many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.
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Análisis Mutacional de ADN , Evolución Molecular , Aptitud Genética , Evasión Inmune , Mutación , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Sitios de Unión , COVID-19/inmunología , COVID-19/virología , Aptitud Genética/genética , Evasión Inmune/genética , Pruebas de Neutralización , Unión Proteica , Dominios Proteicos/genética , SARS-CoV-2/genética , SARS-CoV-2/inmunología , SARS-CoV-2/clasificación , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Internalización del Virus , Células HEK293RESUMEN
Despite the importance of intra-species variants of viruses for causing disease and/or disrupting ecosystem functioning, there is no universally applicable standard to define these. A (natural) gap in whole-genome average nucleotide identity (ANI) values around 95% is commonly used to define species, especially for bacteriophages, but whether a similar gap exists within species that can be used to define intra-species units has not been evaluated yet. Whole-genome comparisons among members of 1,016 bacteriophage (Caudoviricetes) species revealed a region of low frequency of ANI values around 99.2%-99.8%, showing threefold or fewer pairs than expected for an even distribution. This second gap is prevalent in viruses infecting various cultured or uncultured hosts from a variety of environments, although a few exceptions to this pattern were also observed (3.7% of total species) and are likely attributed to cultivation biases or other factors. Similar results were observed for a limited set of eukaryotic viruses that are adequately sampled, including SARS-CoV-2, whose ANI-based clusters matched well with the WHO-defined variants of concern, indicating that our findings from bacteriophages might be more broadly applicable and the ANI-based clusters may represent functionally and/or ecologically distinct units. These units appear to be predominantly driven by (high) ecological cohesiveness coupled to either frequent recombination for bacteriophages or selection and clonal evolution for other viruses such as SARS-CoV-2, indicating that fundamentally different underlying mechanisms could lead to similar diversity patterns. Accordingly, we propose the ANI gap approach outlined above for defining viral intra-species units, for which we propose the term genomovars. IMPORTANCE: Viral species are composed of an ensemble of intra-species variants whose individual dynamics may have major implications for human and animal health and/or ecosystem functioning. However, the lack of universally accepted standards to define these intra-species variants has led researchers to use different approaches for this task, creating inconsistent intra-species units across different viral families and confusion in communication. By comparing hundreds of mostly bacteriophage genomes, we show that there is a widely distributed natural gap in whole-genome average nucleotide identity values in most, but not all, of these species that can be used to define intra-species units. Therefore, these results advance the molecular toolbox for tracking viral intra-species units and should facilitate future epidemiological and environmental studies.
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Bacteriófagos , Genoma Viral , Bacteriófagos/genética , Bacteriófagos/clasificación , Bacteriófagos/aislamiento & purificación , Filogenia , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Humanos , Virus/genética , Virus/clasificación , Variación GenéticaRESUMEN
This retrospective study reports the isolation and characterization of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) from a household cat in South Korea. The cat, which was presented with respiratory symptoms, was identified during a retrospective analysis of samples collected between April 2021 and March 2022. Genomic sequencing revealed that the isolated virus belonged to the Omicron variant (BA.1), coinciding with its global emergence in early 2022. This case study provides evidence for the potential of direct human-to-cat transmission of the Omicron variant in South Korea during its period of widespread circulation. Our findings underscore the importance of continuous monitoring of SARS-CoV-2 in both human and animal populations to track viral evolution and potential spillover events.