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In this work, we have investigated the evolutionary dynamics of a generalist pathogen, e.g., a virus population, that evolves toward specialization in an environment with multiple host types. We have particularly explored under which conditions generalist viral strains may rise in frequency and coexist with specialist strains or even dominate the population. By means of a nonlinear mathematical model and bifurcation analysis, we have determined the theoretical conditions for stability of nine identified equilibria and provided biological interpretation in terms of the infection rates for the viral specialist and generalist strains. By means of a stability diagram, we identified stable fixed points and stable periodic orbits, as well as regions of bistability. For arbitrary biologically feasible initial population sizes, the probability of evolving toward stable solutions is obtained for each point of the analyzed parameter space. This probability map shows combinations of infection rates of the generalist and specialist strains that might lead to equal chances for each type becoming the dominant strategy. Furthermore, we have identified infection rates for which the model predicts the onset of chaotic dynamics. Several degenerate Bogdanov–Takens and zero-Hopf bifurcations are detected along with generalized Hopf and zero-Hopf bifurcations. This manuscript provides additional insights into the dynamical complexity of host–pathogen evolution toward different infection strategies. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 has spread across the world, causing high mortality and unprecedented restrictions on social and economic activity. Policymakers are assessing how best to navigate through the ongoing epidemic, with computational models being used to predict the spread of infection and assess the impact of public health measures. Here, we present OpenABM-Covid19: an agent-based simulation of the epidemic including detailed age-stratification and realistic social networks. By default the model is parameterised to UK demographics and calibrated to the UK epidemic, however, it can easily be re-parameterised for other countries. OpenABM-Covid19 can evaluate non-pharmaceutical interventions, including both manual and digital contact tracing, and vaccination programmes. It can simulate a population of 1 million people in seconds per day, allowing parameter sweeps and formal statistical model-based inference. The code is open-source and has been developed by teams both inside and outside academia, with an emphasis on formal testing, documentation, modularity and transparency. A key feature of OpenABM-Covid19 are its Python and R interfaces, which has allowed scientists and policymakers to simulate dynamic packages of interventions and help compare options to suppress the COVID-19 epidemic. Author summary: Throughout the COVID-19 pandemic, computational modelling has been used to inform key uncertainties facing policymakers such as the number of cases and deaths, hospital capacity, tests and contact tracers. Models need to be: sufficiently complex to yield realistic predictions; computationally efficient to allow calibrations; and easy to use so that various policy mixes can be evaluated. OpenABM-Covid19 is a detailed epidemic model of the spread of COVID-19, simulating every individual in a population. Our model enables scientists and policymakers to quickly compare the effectiveness of non-pharmaceutical interventions like lockdowns, testing, quarantine, and digital and manual contact tracing. The model considers a hypothetical city with a default population of 1 million people whose ages and contact patterns are parameterised according to UK demographics. All of the parameters are openly documented and modifiable so that they can be adapted to fit other countries' data, and refined to match our understanding of COVID-19 as the epidemic progresses. The computer model simulates people's movement between their homes, workplaces, schools, and social interactions. OpenABM-Covid19 is open source and has been developed collaboratively by teams from academia and industry. Its modularity, documentation, testing framework, and accessibility via Python and R have provided validation, invited contributions, and encouraged wide adoption. [ABSTRACT FROM AUTHOR]

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens. [ABSTRACT FROM AUTHOR]

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant. Author summary: The SARS-CoV-2 epidemic in the United Kingdom (UK) has been characterized by the successive transmission of distinct viral variants. Viral variation can impact viral properties, including infectiousness and pathogenicity. These properties may be linked to the amount of virus present in an infected individual. In this study, we examined the association between intra-patient viral burden and a range of factors, including viral variant, using a large, population-representative SARS-CoV-2 survey conducted in the UK. As part of our investigation, we developed a novel method to account for bias in sampled viral burden resulting from the study's sampling methodology. Our findings indicate that viral burden within the host increases with age, is reduced by vaccination, and is influenced by the interplay between vaccination status and viral variant. [ABSTRACT FROM AUTHOR]

The first year of the COVID-19 pandemic put considerable strain on healthcare systems worldwide. In order to predict the effect of the local epidemic on hospital capacity in England, we used a variety of data streams to inform the construction and parameterisation of a hospital progression model, EpiBeds, which was coupled to a model of the generalised epidemic. In this model, individuals progress through different pathways (e.g. may recover, die, or progress to intensive care and recover or die) and data from a partially complete patient-pathway line-list was used to provide initial estimates of the mean duration that individuals spend in the different hospital compartments. We then fitted EpiBeds using complete data on hospital occupancy and hospital deaths, enabling estimation of the proportion of individuals that follow the different clinical pathways, the reproduction number of the generalised epidemic, and to make short-term predictions of hospital bed demand. The construction of EpiBeds makes it straightforward to adapt to different patient pathways and settings beyond England. As part of the UK response to the pandemic, EpiBeds provided weekly forecasts to the NHS for hospital bed occupancy and admissions in England, Wales, Scotland, and Northern Ireland at national and regional scales. Author summary: COVID-19, the disease caused by SARS-CoV-2, leads to a high proportion of cases requiring admission to hospital. Coupled with the high burden of infections worldwide, this put substantial pressure on healthcare systems. To enable public health systems to cope with the high levels of demand, forecasting models are vital. These models enable public health managers to plan their workloads accordingly. Here, we developed EpiBeds, which combines an epidemic model with a model for patient flow through hospitals. By fitting this model to data from England, EpiBeds has been used to provide short-term forecasts of hospital admissions and bed demand weekly throughout the COVID-19 pandemic. In this paper, we describe the motivation behind the structure of EpiBeds, how the model is fitted to data, and report the estimates of the key parameters throughout the pandemic. We then evaluate the performance of EpiBeds by comparing generated forecasts to future data points, finding good agreement between the forecasts and data. [ABSTRACT FROM AUTHOR]

The correct expressions are: Graph HT ht There are a number of errors in the caption for Fig 4, "Adjusted Ct values plotted against different factors". [Extracted from the article]

The article focuses on quantifying severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) transmission. Topics discussed include the use of parameters of epidemic spread to estimate the contribution of different transmission routes, the COVID-19 diagnosis and the early stages of the epidemic in China.