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.

Precautionary breaks: planned, limited duration circuit breaks to control the prevalence of COVID-19 (preprint)

The COVID-19 pandemic in the UK has been characterised by periods of exponential growth and decline, as different non-pharmaceutical interventions (NPIs) are brought into play. During the early uncontrolled phase of the outbreak (early March 2020) there was a period of prolonged exponential growth with epidemiological observations such as hospitalisation doubling every 3-4 days (growth rate r{approx}0.2). The enforcement of strict lockdown measures led to a noticeable decline in all epidemic quantities (r{approx}-0.06) that slowed during the summer as control measures were relaxed (r{approx}-0.02). Since August, infections, hospitalisations and deaths have been rising (precise estimation of the cur-rent growth rate is difficult due to extreme regional heterogeneity and temporal lags between the different epidemiological observations) and various NPIs have been applied locally throughout the UK in response. Controlling any rise in infection is a compromise between public health and societal costs, with more stringent NPIs reducing cases but damaging the economy and restricting freedoms. Currently, NPI imposition is made in response to the epidemiological state, are of indefinite length and are often imposed at short notice, greatly increasing the negative impact. An alternative approach is to consider planned, limited duration periods of strict NPIs aiming to purposefully reduce prevalence before such emergency NPIs are required. These 'precautionary breaks' may offer a means of keeping control of the epidemic, while their fixed duration and the forewarning may limit their society impact. Here, using simple analysis and age-structured models matched to the unfolding UK epidemic, we investigate the action of precautionary breaks. In particular we consider their impact on the prevalence of infection, as well as the total number of predicted hospitalisations and deaths. We find that precautionary breaks provide the biggest gains when the growth rate is low, but offer a much needed brake on increasing infection when the growth rate is higher, potentially allowing other measures (such as contact tracing)to regain control.

Implication of backward contact tracing in the presence of overdispersed transmission in COVID-19 outbreak (preprint)

Unlike forward contact tracing, backward contact tracing identifies the source of newly detected cases. This approach is particularly valuable when there is high individual-level variation in the number of secondary transmissions. By using a simple branching process model, we explored the potential of combining backward contact tracing with more conventional forward contact tracing for control of COVID-19.

Dynamics of SARS-CoV-2 with Waning Immunity in the UK Population (preprint)

The dynamics of immunity are crucial to understanding the long-term patterns of the SARS-CoV-2 pandemic. While the duration and strength of immunity to SARS-CoV-2 is currently unknown, specific antibody titres to related coronaviruses SARS-CoV and MERS-CoV have been shown to wane in recovered individuals, and immunity to seasonal circulating coronaviruses is estimated to be shorter than one year. Using an age-structured, deterministic model, we explore different potential immunity dynamics using contact data from the UK population. In the scenario where immunity to SARS-CoV-2 lasts an average of three months for non-hospitalised individuals, a year for hospitalised individuals, and the effective reproduction number (Rt) after lockdown is 1.2 (our worst case scenario), we find that the secondary peak occurs in winter 2020 with a daily maximum of 409,000 infectious individuals; almost three-fold greater than in a scenario with permanent immunity. Our models suggests that longitudinal serological surveys to determine if immunity in the population is waning will be most informative when sampling takes place from the end of the lockdown until autumn 2020. After this period, the proportion of the population with antibodies to SARS-CoV-2 is expected to increase due to the secondary peak. Overall, our analysis presents considerations for policy makers on the longer term dynamics of SARS-CoV-2 in the UK and suggests that strategies designed to achieve herd immunity may lead to repeated waves of infection if immunity to re-infection is not permanent.

An imperfect tool: COVID-19 'test & trace' success relies on minimising the impact of false negatives and continuation of physical distancing. (preprint)

Background: Following a consistent decline in COVID-19-related deaths in the UK throughout May 2020, it is recognised that contact tracing will be vital to relaxing physical distancing measures. The increasingly evident role of asymptomatic and pre-symptomatic transmission means testing is central to control, but test sensitivity estimates are as low as 65%. Methods: We extend an existing UK-focused branching process model for contact tracing, adding diagnostic testing and refining parameter estimates to demonstrate the impact of poor test sensitivity and suggest mitigation methods. We also investigate the role of super-spreading events, providing estimates of the relationship between infections, cases detected and hospitalisations, and consider how tracing coverage and speed affects outbreak risk. Findings: Incorporating poor sensitivity testing into tracing protocols could reduce efficacy, due to false negative results impacting isolation duration. However, a 7-day isolation period for all negative-testing individuals could mitigate this effect. Similarly, reducing delays to testing following exposure has a negligible impact on the risk of future outbreaks, but could undermine control if negative-testing individuals immediately cease isolating. Even 100% tracing of contacts will miss cases, which could prompt large localised outbreaks if physical distancing measures are relaxed prematurely. Interpretation: It is imperative that test results are interpreted with caution due to high false-negative rates and that contact tracing is used in combination with physical distancing measures. If the risks associated with imperfect test sensitivity are mitigated, we find that contact tracing can facilitate control when the reproduction number with physical distancing, Rs, is less than 1.5.

Segmentation and shielding of the most vulnerable members of the population as elements of an exit strategy from COVID-19 lockdown (preprint)

In this study we demonstrate that the adoption of a segmenting and shielding (S&S) strategy could increase scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of infection. The S&S strategy has an antecedent in the "cocooning" of infants by immunisation of close family members (Forsyth et al., 2015), and forms a pillar of infection, prevention and control (IPC) strategies (RCN, 2017). We are unaware of it being proposed as a major public health initiative previously. We illustrate the S&S strategy using a mathematical model that segments the vulnerable population and their closest contacts, the "shielders". We explore the effects on the epidemic curve of a gradual ramping up of protection for the vulnerable population and a gradual ramping down of restrictions on the non-vulnerable population over a period of 12 weeks after lockdown. The most important determinants of outcome are: i) post-lockdown transmission rates within the general population segment and between the general and vulnerable segments; ii) the fraction of the population in the vulnerable and shielder segments; iii) adherence with need to be protected; and iv) the extent to which population immunity builds up in all segments. We explored the effects of extending the duration of lockdown and faster or slower transition to post-lockdown conditions and, most importantly, the trade-off between increased protection of the vulnerable segment and fewer restrictions on the general population. We illustrate how the potential for the relaxation of restrictions interacts with specific policy objectives. We show that the range of options for relaxation in the general population can be increased by maintaining restrictions on the shielder segment and by intensive routine screening of shielders. We find that the outcome of any future policy is strongly influenced by the contact matrix between segments and the relationships between physical distancing measures and transmission rates. These relationships are difficult to quantify so close monitoring of the epidemic would be essential during and after the exit from lockdown. More generally, S&S has potential applications for any infectious disease for which there are defined proportions of the population who cannot be treated or who are at risk of severe outcomes.