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Omicron surged as a variant of concern in late 2021. Several distinct Omicron variants appeared and overtook each other. We combined variant frequencies and infection estimates from a nowcasting model for each US state to estimate variant-specific infections, attack rates, and effective reproduction numbers (Rt). BA.1 rapidly emerged, and we estimate that it infected 47.7% of the US population before it was replaced by BA.2. We estimate that BA.5 infected 35.7% of the US population, persisting in circulation for nearly 6 months. Other variants-BA.2, BA.4, and XBB-together infected 30.7% of the US population. We found a positive correlation between the state-level BA.1 attack rate and social vulnerability and a negative correlation between the BA.1 and BA.2 attack rates. Our findings illustrate the complex interplay between viral evolution, population susceptibility, and social factors during the Omicron emergence in the US.
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COVID-19 , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , COVID-19/virología , COVID-19/epidemiología , Humanos , Estados Unidos/epidemiología , Genoma Viral , Genómica/métodosRESUMEN
Global dengue cases rapidly rose to record levels in 2023-24. We investigated this trend in Valle del Cauca, Colombia to determine if specific dengue virus serotypes or lineages were responsible for the large outbreak. We detected all four serotypes and multiple lineages, suggesting that other factors, such as climatic conditions, are likely responsible.
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BACKGROUND: Dengue fever remains a significant public health challenge in tropical and subtropical regions, with its transmission dynamics being influenced by both environmental factors and human mobility. The Dominican Republic, a biodiversity hotspot in the Caribbean, has experienced recurrent dengue outbreaks, yet detailed understanding of the virus's transmission pathways and the impact of climatic factors remains limited. This study aims to elucidate the recent transmission dynamics of the dengue virus (DENV) in the Dominican Republic, utilizing a combination of genomic sequencing and epidemiological data analysis, alongside an examination of historical climate patterns. METHODS: We conducted a comprehensive study involving the genomic sequencing of DENV samples collected from patients across different regions of the Dominican Republic over a two-year period. Phylogenetic analyses were performed to identify the circulation of DENV lineages and to trace transmission pathways. Epidemiological data were integrated to analyze trends in dengue incidence and distribution. Additionally, we integrated historical climate data spanning several decades to assess trends in temperature and their potential impact on DENV transmission potential. RESULTS: Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. CONCLUSION: This multidisciplinary study reveals intricate patterns of dengue virus transmission in the Dominican Republic, characterized by the co-circulation of multiple DENV lineages and a novel transmission pathway. The observed correlation between rising temperatures and increased dengue transmission potential emphasizes the need for integrated climate-informed strategies in dengue control efforts. Our findings offer critical insights for public health authorities in the Dominican Republic and similar settings, guiding resource allocation and the development of preparedness strategies to mitigate the impacts of climate change on dengue transmission.
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Clima , Virus del Dengue , Dengue , Filogenia , Serogrupo , República Dominicana/epidemiología , Dengue/epidemiología , Dengue/transmisión , Dengue/virología , Humanos , Virus del Dengue/genética , Virus del Dengue/clasificación , Brotes de EnfermedadesRESUMEN
Circulating bat coronaviruses represent a pandemic threat. However, our understanding of bat coronavirus pathogenesis and transmission potential is limited by the lack of phenotypically characterized strains. We created molecular clones for the two closest known relatives of SARS-CoV-2, BANAL-52 and BANAL-236. We demonstrated that BANAL-CoVs and SARS-CoV-2 have similar replication kinetics in human bronchial epithelial cells. However, BANAL-CoVs have impaired replication in human nasal epithelial cells and in the upper airway of mice. We also observed reduced pathogenesis in mice and diminished transmission in hamsters. Further, we observed that diverse bat coronaviruses evade interferon and downregulate major histocompatibility complex class I. Collectively, our study demonstrates that despite high genetic similarity across bat coronaviruses, prediction of pandemic potential of a virus necessitates functional characterization. Finally, the restriction of bat coronavirus replication in the upper airway highlights that transmission potential and innate immune restriction can be uncoupled in this high-risk family of emerging viruses.
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COVID-19 , Quirópteros , Inmunidad Innata , SARS-CoV-2 , Replicación Viral , Animales , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Quirópteros/virología , Quirópteros/inmunología , COVID-19/transmisión , COVID-19/virología , COVID-19/inmunología , Ratones , Cricetinae , Evasión Inmune , Células Epiteliales/virología , Células Epiteliales/inmunología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Coronavirus/inmunología , Coronavirus/genética , Coronavirus/clasificación , Coronavirus/fisiología , Coronavirus/patogenicidad , Línea Celular , FemeninoRESUMEN
BACKGROUND: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. RESULTS: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. CONCLUSIONS: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.
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Virus del Dengue , Genoma Viral , Serogrupo , Secuenciación Completa del Genoma , Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Virus del Dengue/clasificación , Secuenciación Completa del Genoma/métodos , Humanos , Genotipo , Dengue/virología , Dengue/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , ARN Viral/genéticaRESUMEN
Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here we propose adding two sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present an assignment tool to show that the proposed lineages are useful for regional, national and sub-national discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at: dengue-lineages.org.
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Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.
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Virus del Dengue , Dengue , Brotes de Enfermedades , Serogrupo , Viaje , Virus del Dengue/genética , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Dengue/epidemiología , Dengue/virología , Dengue/transmisión , Humanos , Región del Caribe/epidemiología , Viaje/estadística & datos numéricos , Filogenia , Monitoreo EpidemiológicoRESUMEN
SARS-CoV-2 antibody levels may serve as a correlate for immunity and could inform optimal booster timing. The relationship between antibody levels and protection from infection was evaluated in vaccinated individuals from the US National Basketball Association who had antibody levels measured at a single time point from September 12, 2021, to December 31, 2021. Cox proportional hazards models were used to estimate the risk of infection within 90 days of serologic testing by antibody level (<250, 250-800, and >800 AU/mL1 ), adjusting for age, time since last vaccine dose, and history of SARS-CoV-2 infection. Individuals were censored on date of booster receipt. The analytic cohort comprised 2323 individuals and was 78.2% male, 68.1% aged ≤40 years, and 56.4% vaccinated (primary series) with the Pfizer-BioNTech mRNA vaccine. Among the 2248 (96.8%) individuals not yet boosted at antibody testing, 77% completed their primary vaccine series 4-6 months before testing and the median (interquartile range) antibody level was 293.5 (interquartile range: 121.0-740.5) AU/mL. Those with levels <250 AU/mL (adj hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.5-3.7) and 250-800 AU/mL (adj HR: 1.5; 95% CI: 0.98-2.4) had greater infection risk compared to those with levels >800 AU/mL. Antibody levels could inform individual COVID-19 risk and booster scheduling.
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Baloncesto , COVID-19 , Vacunas , Humanos , Masculino , Femenino , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos AntiviralesRESUMEN
SARS-CoV-2 causes persistent infections in a subset of individuals, which is a major clinical and public health problem that should be prioritised for further investigation for several reasons. First, persistent SARS-CoV-2 infection often goes unrecognised, and therefore might affect a substantial number of people, particularly immunocompromised individuals. Second, the formation of tissue reservoirs (including in non-respiratory tissues) might underlie the pathophysiology of the persistent SARS-CoV-2 infection and require new strategies for diagnosis and treatment. Finally, persistent SARS-CoV-2 replication, particularly in the setting of suboptimal immune responses, is a possible source of new, divergent virus variants that escape pre-existing immunity on the individual and population levels. Defining optimal diagnostic and treatment strategies for patients with persistent virus replication and monitoring viral evolution are therefore urgent medical and public health priorities.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Replicación Viral , Huésped InmunocomprometidoRESUMEN
We employ a multidisciplinary approach, integrating genomics and epidemiology, to uncover recent dengue virus transmission dynamics in the Dominican Republic. Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. These findings provide information for targeted interventions and resource allocation, informing as well towards preparedness strategies for public health agencies in mitigating climate and geo-related dengue risks.
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West Nile virus (WNV) is an emerging mosquito-borne pathogen in Europe where it represents a new public health threat. While climate change has been cited as a potential driver of its spatial expansion on the continent, a formal evaluation of this causal relationship is lacking. Here, we investigate the extent to which WNV spatial expansion in Europe can be attributed to climate change while accounting for other direct human influences such as land-use and human population changes. To this end, we trained ecological niche models to predict the risk of local WNV circulation leading to human cases to then unravel the isolated effect of climate change by comparing factual simulations to a counterfactual based on the same environmental changes but a counterfactual climate where long-term trends have been removed. Our findings demonstrate a notable increase in the area ecologically suitable for WNV circulation during the period 1901-2019, whereas this area remains largely unchanged in a no-climate-change counterfactual. We show that the drastic increase in the human population at risk of exposure is partly due to historical changes in population density, but that climate change has also been a critical driver behind the heightened risk of WNV circulation in Europe.
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Culicidae , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Animales , Humanos , Fiebre del Nilo Occidental/epidemiología , Cambio Climático , Europa (Continente)/epidemiologíaRESUMEN
During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.
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Virus del Dengue , Dengue , Humanos , Virus del Dengue/genética , Dengue/epidemiología , Florida/epidemiología , Viaje , Secuencia de Bases , Genotipo , Serogrupo , FilogeniaRESUMEN
West Nile virus is one of the most widespread mosquito-borne zoonotic viruses, with unique transmission dynamics in various parts of the world. Genomic surveillance has provided important insights in the global patterns of West Nile virus emergence and spread. In Europe, multiple West Nile virus lineages have been isolated, with lineage 1a and 2 being the main lineages responsible for human infections. In contrast to North America, where a single introduction of lineage 1a resulted in the virus establishing itself in a new continent, at least 13 introductions of lineages 1a and 2 have occurred into Europe, which is likely a vast underestimation of the true number of introductions. Historically, lineage 1a was the main lineage circulating in Europe, but since the emergence of lineage 2 in the early 2000s, the latter has become the predominant lineage. This shift in West Nile virus lineage prevalence has been broadly linked to the expansion of the virus into northerly temperate regions, where autochthonous cases in animals and humans have been reported in Germany and The Netherlands. Here, we discuss how genomic analysis has increased our understanding of the epidemiology of West Nile virus in Europe, and we present a global Nextstrain build consisting of publicly available West Nile virus genomes (https://nextstrain.org/community/grubaughlab/WNV-Global). Our results elucidate recent insights in West Nile virus lineage dynamics in Europe, and discuss how expanded programs can fill current genomic surveillance gaps.
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Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.
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Diverse mammalian species display susceptibility to and infection with SARS-CoV-2. Potential SARS-CoV-2 spillback into rodents is understudied despite their host role for numerous zoonoses and human proximity. We assessed exposure and infection among white-footed mice (Peromyscus leucopus) in Connecticut, USA. We observed 1% (6/540) wild-type neutralizing antibody seroprevalence among 2020-2022 residential mice with no cross-neutralization of variants. We detected no SARS-CoV-2 infections via RT-qPCR, but identified non-SARS-CoV-2 betacoronavirus infections via pan-coronavirus PCR among 1% (5/468) of residential mice. Sequencing revealed two divergent betacoronaviruses, preliminarily named Peromyscus coronavirus-1 and -2. Both belong to the Betacoronavirus 1 species and are ~90% identical to the closest known relative, Porcine hemagglutinating encephalomyelitis virus. Low SARS-CoV-2 seroprevalence suggests white-footed mice may not be sufficiently susceptible or exposed to SARS-CoV-2 to present a long-term human health risk. However, the discovery of divergent, non-SARS-CoV-2 betacoronaviruses expands the diversity of known rodent coronaviruses and further investigation is required to understand their transmission extent.
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Since its emergence in 2016, extensively drug resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) has become the dominant cause of typhoid fever in Pakistan. The establishment of sustained XDR S. Typhi transmission in other countries represents a major public health threat. We show that the annual volume of air travel from Pakistan strongly discriminates between countries that have and have not imported XDR S. Typhi in the past, and identify a significant association between air travel volume and the rate of between-country movement of the H58 haplotype of S. Typhi from fitted phylogeographic models. Applying these insights, we analyze flight itinerary data cross-referenced with model-based estimates of typhoid fever incidence to identify the countries at highest risk of importation and sustained onward transmission of XDR S. Typhi. Future outbreaks of XDR typhoid are most likely to occur in countries that can support efficient local S. Typhi transmission and have strong travel links to regions with ongoing XDR typhoid outbreaks (currently Pakistan). Public health activities to track and mitigate the spread of XDR S. Typhi should be prioritized in these countries.
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Viaje en Avión , Fiebre Tifoidea , Humanos , Salmonella typhi/genética , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/tratamiento farmacológico , Antibacterianos/uso terapéutico , Brotes de EnfermedadesRESUMEN
Background: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. Results: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 101-102 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. Conclusions: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.
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The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we identified 71 individuals with two well-sampled SARS-CoV-2 infections between March 11th, 2020, and July 28th, 2022. We compared the SARS-CoV-2 viral kinetics of first vs. second infections in this group, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a faster clearance time. Furthermore, a person's relative (rank-order) viral clearance time, compared to others infected with the same variant, was roughly conserved across first and second infections, so that individuals who had a relatively fast clearance time in their first infection also tended to have a relatively fast clearance time in their second infection (Spearman correlation coefficient: 0.30, 95% credible interval (0.12, 0.46)). These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person's relative ability to clear SARS-CoV-2 infection that persists across sequential infections.
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COVID-19 , Humanos , SARS-CoV-2 , Prueba de COVID-19 , Proyectos de Investigación , CinéticaRESUMEN
Several aspects of mosquito ecology that are important for vectored disease transmission and control have been difficult to measure at epidemiologically important scales in the field. In particular, the ability to describe mosquito population structure and movement rates has been hindered by difficulty in quantifying fine-scale genetic variation among populations. The mosquito virome represents a possible avenue for quantifying population structure and movement rates across multiple spatial scales. Mosquito viromes contain a diversity of viruses, including several insect-specific viruses (ISVs) and "core" viruses that have high prevalence across populations. To date, virome studies have focused on viral discovery and have only recently begun examining viral ecology. While nonpathogenic ISVs may be of little public health relevance themselves, they provide a possible route for quantifying mosquito population structure and dynamics. For example, vertically transmitted viruses could behave as a rapidly evolving extension of the host's genome. It should be possible to apply established analytical methods to appropriate viral phylogenies and incidence data to generate novel approaches for estimating mosquito population structure and dispersal over epidemiologically relevant timescales. By studying the virome through the lens of spatial and genomic epidemiology, it may be possible to investigate otherwise cryptic aspects of mosquito ecology. A better understanding of mosquito population structure and dynamics are key for understanding mosquito-borne disease ecology and methods based on ISVs could provide a powerful tool for informing mosquito control programs.