Real-time COVID-19 hospital admissions forecasting with leading indicators and ensemble methods in England (preprint)

Hospitalisations from COVID-19 with Omicron sub-lineages have put a sustained pressure on the English healthcare system. Understanding the expected healthcare demand enables more effective and timely planning from public health. We collect syndromic surveillance sources, which include online search data, NHS 111 telephonic and online triages. Incorporating this data we explore generalised additive models, generalised linear mixed-models, penalised generalised linear models and model ensemble methods to forecast over a two-week forecast horizon at an NHS Trust level. Furthermore, we showcase how model combinations improve forecast scoring through a mean ensemble, weighted ensemble, and ensemble by regression. Validated over multiple Omicron waves, at different spatial scales, we show that leading indicators can improve performance of forecasting models, particularly at epidemic changepoints. Using a variety of scoring rules, we show that ensemble approaches outperformed all individual models, providing higher performance at a 21-day window than the corresponding individual models at 14-days. We introduce a modelling structure used by public health officials in England in 2022 to inform NHS healthcare strategy and policy decision making. This paper explores the significance of ensemble methods to improve forecasting performance and how novel syndromic surveillance can be practically applied in epidemic forecasting.

Understanding the leading indicators of hospital admissions from COVID-19 across successive waves in the UK (preprint)

Following the UK Government's Living with COVID-19 Strategy and the end of universal testing, hospital admissions are an increasingly important measure of COVID-19 pandemic pressure. Understanding leading indicators of admissions at National Health Service (NHS) Trust, regional and national geographies help health services plan capacity needs and prepare for ongoing pressures. We explored the spatio-temporal relationships of leading indicators of hospital pressure across successive waves of SARS-CoV-2 incidence in England. This includes an analysis of internet search volume values from Google Trends, NHS triage calls and online queries, the NHS COVID-19 App, lateral flow devices and the ZOE App. Data sources were analysed for their feasibility as leading indicators using linear and non-linear methods; granger causality, cross correlations and dynamic time warping at fine spatial scales. Consistent temporal and spatial relationships were found for some of the leading indicators assessed across resurgent waves of COVID-19. Google Trends and NHS queries consistently led admissions in over 70% of Trusts, with lead times ranging from 5-20 days, whereas an inconsistent relationship was found for the ZOE app, NHS COVID-19 App, and rapid testing, that diminished with granularity, showing limited autocorrelation of leads between -7 to 7 days. This work shows that novel syndromic surveillance data has utility for understanding the expected hospital burden at fine spatial scales. The analysis shows at low level geographies that some surveillance sources can predict hospital admissions, though care must be taken in relying on the lead times and consistency between waves.

The role of regular asymptomatic testing in reducing the impact of a COVID-19 wave (preprint)

Testing for infection with SARS-CoV-2 is an important intervention in reducing onwards transmission of COVID-19, particularly when combined with the isolation and contact-tracing of positive cases. Many countries with the capacity to do so have made use of lab-processed Polymerase Chain Reaction (PCR) testing targeted at individuals with symptoms and the contacts of confirmed cases. Alternatively, Lateral Flow Tests (LFTs) are able to deliver a result quickly, without lab-processing and at a relatively low cost. Their adoption can support regular mass asymptomatic testing, allowing earlier detection of infection and isolation of infectious individuals. In this paper we extend and apply the agent-based epidemic modelling framework Covasim to explore the impact of regular asymptomatic testing on the peak and total number of infections in an emerging COVID-19 wave. We explore testing with LFTs at different frequency levels within a population with high levels of immunity and with background symptomatic PCR testing, case isolation and contact tracing for testing. The effectiveness of regular asymptomatic testing was compared with `lockdown' interventions seeking to reduce the number of non-household contacts across the whole population through measures such as mandating working from home and restrictions on gatherings. Since regular asymptomatic testing requires only those with a positive result to reduce contact, while lockdown measures require the whole population to reduce contact, any policy decision that seeks to trade off harms from infection against other harms will not automatically favour one over the other. Our results demonstrate that, where such a trade off is being made, at moderate rates of early exponential growth regular asymptomatic testing has the potential to achieve significant infection control without the wider harms associated with additional lockdown measures.

Public perceptions and interactions with UK COVID-19 Test, Trace and Isolate policies, and implications for pandemic infectious disease modelling (preprint)

The efforts to contain SARS-CoV-2 and reduce the impact of COVID-19 have been supported by Test, Trace and Isolate (TTI) systems in many settings, including the United Kingdom. The mathematical models underlying policy decisions about TTI make assumptions about behaviour in the context of a rapidly unfolding and changeable emergency. This study investigates the reported behaviours of UK citizens in July 2021, assesses them against how a set of TTI processes are conceptualised and represented in models and then interprets the findings with modellers who have been contributing evidence to TTI policy. We report on testing practices, including the uses of and trust in different types of testing, and the challenges of testing and isolating faced by different demographic groups. The study demonstrates the potential of input from members of the public to benefit the modelling process, from guiding the choice of research questions, influencing choice of model structure, informing parameter ranges and validating or challenging assumptions, to highlighting where model assumptions are reasonable or where their poor reflection of practice might lead to uninformative results. We conclude that deeper engagement with members of the public should be integrated at regular stages of public health intervention modelling.

Diversity of symptom phenotypes in SARS-CoV-2 community infections observed in multiple large datasets (preprint)

Through the use of cutting-edge unsupervised classification techniques from statistics and machine learning, we characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases. We first analyse each dataset in isolation and across age bands, before using methods that allow us to compare multiple datasets. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. In this way, we are able to demonstrate the deep structure of symptoms of COVID-19 without usual biases due to study design. This is expected to have implications for the identification and management of community SARS-CoV-2 cases and could be further applied to symptom-based management of other diseases and syndromes.

Using a household structured branching process to analyse contact tracing in the SARS-CoV-2 pandemic (preprint)

We explore strategies of contact tracing, case isolation and quarantine of exposed contacts to control the SARS-CoV-2 epidemic using a branching process model with household structure. This structure reflects higher transmission risks among household members than among non-household members, and is also the level at which physical distancing policies have been applied. We explore implementation choices that make use of household structure, and investigate strategies including two-step tracing, backwards tracing, smartphone tracing and tracing upon symptom report rather than test results. The primary model outcome is the effect on the growth rate of the epidemic under contact tracing in combination with different levels of physical distancing, and we investigate epidemic extinction times to indicate the time period over which interventions must be sustained. We consider effects of non-uptake of isolation/quarantine, non-adherence, and declining recall of contacts over time. We find that compared to self-isolation of cases but no contact tracing, a household-based contact tracing strategy allows for some relaxation of physical distancing measures; however, it is unable to completely control the epidemic in the absence of other measures. Even assuming no imported cases and sustainment of moderate distancing, testing and tracing efforts, the time to bring the epidemic to extinction could be in the order of months to years.

Using statistics and mathematical modelling to understand infectious disease outbreaks: COVID-19 as an example (preprint)

During an infectious disease outbreak, biases in the data and complexities of the underlying dynamics pose significant challenges in mathematically modelling the outbreak and designing policy. Motivated by the ongoing response to COVID-19, we provide a toolkit of statistical and mathematical models beyond the simple SIR-type differential equation models for analysing the early stages of an outbreak and assessing interventions. In particular, we focus on parameter estimation in the presence of known biases in the data, and the effect of non-pharmaceutical interventions in enclosed subpopulations, such as households and care homes. We illustrate these methods by applying them to the COVID-19 pandemic.

Challenges in control of Covid-19: short doubling time and long delay to effect of interventions (preprint)

The unconstrained growth rate of COVID-19 is crucial for measuring the impact of interventions, assessing worst-case scenarios, and calibrating mathematical models for policy planning. However, robust estimates are limited, with scientific focus on the time-insensitive basic reproduction number R0. Using multiple countries, data streams and methods, we consistently estimate that European COVID-19 cases doubled every three days when unconstrained, with the impact of physical distancing interventions typically seen about nine days after implementation, during which time cases grew eight-fold. The combination of fast growth and long detection delays explains the struggle in countries' response better than large values of R0 alone, and warns against relaxing physical distancing measures too quickly. Testing and tracing are fundamental in shortening such delays, thus preventing cases from escalating unnoticed.

Challenges in control of Covid-19: short doubling time and long delay to effect of interventions (preprint)

Early assessments of the spreading rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but more reliable inferences can now be made. Here, we estimate from European data that COVID-19 cases are expected to double initially every three days, until social distancing interventions slow this growth, and that the impact of such measures is typically only seen nine days - i.e. three doubling times - after their implementation. We argue that such temporal patterns are more critical than precise estimates of the basic reproduction number for initiating interventions. This observation has particular implications for the low- and middle-income countries currently in the early stages of their local epidemics.