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122 result(s) for "Haw, David"
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Using real-time data to guide decision-making during an influenza pandemic: A modelling analysis
Influenza pandemics typically occur in multiple waves of infection, often associated with initial emergence of a novel virus, followed (in temperate regions) by a resurgence accompanying the onset of the annual influenza season. Here, we examined whether data collected from an initial pandemic wave could be informative, for the need to implement non-pharmaceutical measures in any resurgent wave. Drawing from the 2009 H1N1 pandemic in 10 states in the USA, we calibrated simple mathematical models of influenza transmission dynamics to data for laboratory confirmed hospitalisations during the initial ‘spring’ wave. We then projected pandemic outcomes (cumulative hospitalisations) during the fall wave, and compared these projections with data. Model results showed reasonable agreement for all states that reported a substantial number of cases in the spring wave. Using this model we propose a probabilistic decision framework that can be used to determine the need for preemptive measures such as postponing school openings, in advance of a fall wave. This work illustrates how model-based evidence synthesis, in real-time during an early pandemic wave, could be used to inform timely decisions for pandemic response.
Strong spatial embedding of social networks generates nonstandard epidemic dynamics independent of degree distribution and clustering
Some directly transmitted human pathogens, such as influenza and measles, generate sustained exponential growth in incidence and have a high peak incidence consistent with the rapid depletion of susceptible individuals. Many do not. While a prolonged exponential phase typically arises in traditional disease-dynamic models, current quantitative descriptions of nonstandard epidemic profiles are either abstract, phenomenological, or rely on highly skewed offspring distributions in network models. Here, we create large socio-spatial networks to represent contact behavior using human population-density data, a previously developed fitting algorithm, and gravity-like mobility kernels. We define a basic reproductive number R₀ for this system, analogous to that used for compartmental models. Controlling for R₀, we then explore networks with a household–workplace structure in which between-household contacts can be formed with varying degrees of spatial correlation, determined by a single parameter from the gravity-like kernel. By varying this single parameter and simulating epidemic spread, we are able to identify how more frequent local movement can lead to strong spatial correlation and, thus, induce subexponential outbreak dynamics with lower, later epidemic peaks. Also, the ratio of peak height to final size was much smaller when movement was highly spatially correlated. We investigate the topological properties of our networks via a generalized clustering coefficient that extends beyond immediate neighborhoods, identifying very strong correlations between fourth-order clustering and nonstandard epidemic dynamics. Our results motivate the observation of both incidence and socio-spatial human behavior during epidemics that exhibit nonstandard incidence patterns.
Differential mobility and local variation in infection attack rate
Infectious disease transmission is an inherently spatial process in which a host's home location and their social mixing patterns are important, with the mixing of infectious individuals often different to that of susceptible individuals. Although incidence data for humans have traditionally been aggregated into low-resolution data sets, modern representative surveillance systems such as electronic hospital records generate high volume case data with precise home locations. Here, we use a gridded spatial transmission model of arbitrary resolution to investigate the theoretical relationship between population density, differential population movement and local variability in incidence. We show analytically that a uniform local attack rate is typically only possible for individual pixels in the grid if susceptible and infectious individuals move in the same way. Using a population in Guangdong, China, for which a robust quantitative description of movement is available (a travel kernel), and a natural history consistent with pandemic influenza; we show that local cumulative incidence is positively correlated with population density when susceptible individuals are more connected in space than infectious individuals. Conversely, under the less intuitively likely scenario, when infectious individuals are more connected, local cumulative incidence is negatively correlated with population density. The strength and direction of correlation changes sign for other kernel parameter values. We show that simulation models in which it is assumed implicitly that only infectious individuals move are assuming a slightly unusual specific correlation between population density and attack rate. However, we also show that this potential structural bias can be corrected by using the appropriate non-isotropic kernel that maps infectious-only code onto the isotropic dual-mobility kernel. These results describe a precise relationship between the spatio-social mixing of infectious and susceptible individuals and local variability in attack rates. More generally, these results suggest a genuine risk that mechanistic models of high-resolution attack rate data may reach spurious conclusions if the precise implications of spatial force-of-infection assumptions are not first fully characterized, prior to models being fit to data.
Dynamics of SARS-CoV-2 infection hospitalisation and infection fatality ratios over 23 months in England
The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. Reliable estimates of the infection fatality ratio (IFR) and infection hospitalisation ratio (IHR) along with the time-delay between infection and hospitalisation/death can inform forecasts of the numbers/timing of severe outcomes and allow healthcare services to better prepare for periods of increased demand. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in England approximately monthly from May 2020 to March 2022. Here, we analyse the changing relationship between prevalence of swab positivity and the IFR and IHR over this period in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models, and Bayesian P-spline models. We analyse data for all age groups together, as well as in 2 subgroups: those aged 65 and over and those aged 64 and under. Additionally, we analysed the relationship between swab positivity and daily case numbers to estimate the case ascertainment rate of England’s mass testing programme. During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late 2021/early 2022, the IFR and IHR had both decreased to 0.097% and 0.76%, respectively. The average case ascertainment rate over the entire duration of the study was estimated to be 36.1%, but there was some significant variation in continuous estimates of the case ascertainment rate. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta’s emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late 2021/early 2022, these time-lags had decreased to 7 days for hospitalisations and 18 days for deaths. Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on the IHR and IFR. As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship between infection, hospitalisation, and death and hence provide vital information for healthcare provision and utilisation.
Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England
The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England’s Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the ‘new normal’. This study presents data from the REACT-1 SARS-CoV-2 community sampling study in England from November 2021 to March 2022. They show that the Omicron variant peaked in January with a prevalence of ~7% and that the BA.2 sublineage had a 1.5x higher reproduction number compared to other Omicron sublineages.
Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England
Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n = 102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R = 0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R = 1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron. The REACT-1 study measures the community prevalence of SARS-CoV-2 in England through repeated cross-sectional surveys. Here, the authors present data from REACT-1 that document the increase in infection prevalence, particularly among children, associated with the Omicron variant in January 2022.
Trends in SARS-CoV-2 infection prevalence during England’s roadmap out of lockdown, January to July 2021
Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards. We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence. On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions. Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was offset by the effects of vaccination and also affected by the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups. High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was effective at reducing risk of infection with school holidays/closures playing a significant part.
Optimizing social and economic activity while containing SARS-CoV-2 transmission using DAEDALUS
To study the trade-off between economic, social and health outcomes in the management of a pandemic, DAEDALUS integrates a dynamic epidemiological model of SARS-CoV-2 transmission with a multi-sector economic model, reflecting sectoral heterogeneity in transmission and complex supply chains. The model identifies mitigation strategies that optimize economic production while constraining infections so that hospital capacity is not exceeded but allowing essential services, including much of the education sector, to remain active. The model differentiates closures by economic sector, keeping those sectors open that contribute little to transmission but much to economic output and those that produce essential services as intermediate or final consumption products. In an illustrative application to 63 sectors in the United Kingdom, the model achieves an economic gain of between £161 billion (24%) and £193 billion (29%) compared to a blanket lockdown of non-essential activities over six months. Although it has been designed for SARS-CoV-2, DAEDALUS is sufficiently flexible to be applicable to pandemics with different epidemiological characteristics.
Health inequalities in risk of SARS-CoV-2 infection in England’s second wave: population-based cross-sectional analysis from the REACT-1 study
ObjectivesThe rapid spread of SARS-CoV-2 infection caused high levels of hospitalisation and deaths in late 2020 and early 2021 during the second wave in England. COVID-19 disease during this period was associated with marked health inequalities across ethnic and sociodemographic subgroups. In this paper, we aim to investigate and quantify inequalities in the risk of SARS-CoV-2 infection across ethnic and sociodemographic subgroups during a key period before widespread vaccination, thereby identifying the populations that bore a disproportionate burden of risk.MethodsWe analysed risk factors for test-positivity for SARS-CoV-2, based on self-administered throat and nose swabs in the community during rounds 5–10 of the REal-time Assessment of Community Transmission-1 (REACT-1) study between 18 September 2020 and 30 March 2021.ResultsCompared with the White ethnicity, people of Asian and the Black ethnicity had a higher risk of infection during rounds 5–10, with odds of 1.45 (1.27, 1.66) and 1.34 (1.11, 1.63), respectively, adjusted for demographic factors including age, sex, region, key work status, ethnicity and deprivation. Among ethnic subgroups, the highest and the second-highest odds were found in Bangladeshi and Pakistani participants at 3.28 (2.24, 4.80) and 2.12 (1.70, 2.64), respectively, when compared with the White British participants. People in larger (compared with smaller) households had higher odds of infection. Healthcare workers with direct patient contact and care home workers showed higher odds of infection compared with other essential/key workers. Additionally, the odds of infection among participants in public-facing activities or settings were greater than among those not working in those activities or settings.ConclusionOur findings highlight the differences in the risk of SARS-CoV-2 infection in a global north population during a period when the risk of infection was high, and there were substantial levels of social mixing. Planning for future waves of severe respiratory pathogens should include policies to reduce inequality in the risk of infection by ethnicity, household size and occupational activity in order to reduce inequality in disease.
Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo
On 21 February 2020, a resident of the municipality of Vo’, a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 1 . This was the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province 2 . In response, the regional authorities imposed the lockdown of the whole municipality for 14 days 3 . Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo’ at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1–3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8–1.8%). Notably, 42.5% (95% CI: 31.5–54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9–9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections ( P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon–Mann–Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures. The authors describe the prevalence of SARS-CoV-2 infection, viral load and the frequency of symptomatic versus asymptomatic and presymptomatic infection in an Italian town, before and after a strict 14-day lockdown.