Which lockdowns are the best lockdowns? Optimal interventions and the trolley problem in heterogeneous populations (preprint)

Interventions to mitigate the spread of infectious diseases, while succeeding in their goal, have economic and social costs associated with them. These limit the duration and intensity of the interventions. We study a class of interventions which reduce the reproduction number and find the optimal strength of the intervention which minimises the attack rate of an immunity inducing infection. The intervention works by eliminating the overshoot part of an epidemic, and avoids a second-wave of infections. We extend the framework by considering a heterogeneous population and find that the optimal intervention can pose an ethical dilemma for decision and policy makers. This ethical dilemma is shown to be analogous to the trolley problem and we discuss how the dilemma can be avoided.

Dynamic Survival Analysis for non-Markovian Epidemic Models (preprint)

We present a new method for analyzing stochastic epidemic models under minimal assumptions. The method, dubbed DSA, is based on a simple yet powerful observation, namely that population-level mean-field trajectories described by a system of PDE may also approximate individual-level times of infection and recovery. This idea gives rise to a certain non-Markovian agent-based model and provides an agent-level likelihood function for a random sample of infection and/or recovery times. Extensive numerical analyses on both synthetic and real epidemic data from the FMD in the United Kingdom and the COVID-19 in India show good accuracy and confirm method's versatility in likelihood-based parameter estimation. The accompanying software package gives prospective users a practical tool for modeling, analyzing and interpreting epidemic data with the help of the DSA approach.

Beyond COVID-19: Network science and sustainable exit strategies (preprint)

On May $28^{th}$ and $29^{th}$, a two day workshop was held virtually, facilitated by the Beyond Center at ASU and Moogsoft Inc. The aim was to bring together leading scientists with an interest in Network Science and Epidemiology to attempt to inform public policy in response to the COVID-19 pandemic. Epidemics are at their core a process that progresses dynamically upon a network, and are a key area of study in Network Science. In the course of the workshop a wide survey of the state of the subject was conducted. We summarize in this paper a series of perspectives of the subject, and where the authors believe fruitful areas for future research are to be found.

Covid-19 and Flattening the Curve: a Feedback Control Perspective (preprint)

Many of the control policies that were put into place during the Covid-19 pandemic had a common goal: to flatten the curve of the number of infected people so that its peak remains under a critical threshold. This letter considers the challenge of engineering a strategy that enforces such a goal using control theory. We introduce a simple formulation of the optimal flattening problem, and provide a closed form solution.This is augmented through nonlinear closed loop tracking of the nominal solution, with the aim of ensuring close-to-optimal performance under uncertain conditions. A key contribution ofthis paper is to provide validation of the method with extensive and realistic simulations in a Covid-19 scenario, with particular focus on the case of Codogno - a small city in Northern Italy that has been among the most harshly hit by the pandemic.

The impact of network properties and mixing on control measures and disease-induced herd immunity in epidemic models: a mean-field model perspective (preprint)

The contact structure of a population plays an important role in transmission of infection. Many ``structured models'' capture aspects of the contact structure through an underlying network or a mixing matrix. An important observation in such models, is that once a fraction $1-1/\mathcal{R}_0$ has been infected, the residual susceptible population can no longer sustain an epidemic. A recent observation of some structured models is that this threshold can be crossed with a smaller fraction of infected individuals, because the disease acts like a targeted vaccine, preferentially immunizing higher-risk individuals who play a greater role in transmission. Therefore, a limited ``first wave'' may leave behind a residual population that cannot support a second wave once interventions are lifted. In this paper, we systematically analyse a number of mean-field models for networks and other structured populations to address issues relevant to the Covid-19 pandemic. In particular, we consider herd-immunity under several scenarios. We confirm that, in networks with high degree heterogeneity, the first wave confers herd-immunity with significantly fewer infections than equivalent models with lower degree heterogeneity. However, if modelling the intervention as a change in the contact network, then this effect might become more subtle. Indeed, modifying the structure can shield highly connected nodes from becoming infected during the first wave and make the second wave more substantial. We confirm this finding by using an age-structured compartmental model parameterised with real data and comparing lockdown periods implemented either as a global scaling of the mixing matrix or age-specific structural changes. We find that results regarding herd immunity levels are strongly dependent on the model, the duration of lockdown and how lockdown is implemented.

Key Questions for Modelling COVID-19 Exit Strategies (preprint)

Combinations of intense non-pharmaceutical interventions ('lockdowns') were introduced in countries worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement lockdown exit strategies that allow restrictions to be relaxed while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, will allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. The roadmap requires a global collaborative effort from the scientific community and policy-makers, and is made up of three parts: i) improve estimation of key epidemiological parameters; ii) understand sources of heterogeneity in populations; iii) focus on requirements for data collection, particularly in Low-to-Middle-Income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.

The timing of one-shot interventions for epidemic control (preprint)

The apparent early success in China's large-scale intervention to control the COVID-19 epidemic has led to interest in whether other countries can replicate it as well as concerns about a resurgence of the epidemic if or when China relaxes the interventions. In this paper we look at the impact of a single short-term intervention on an epidemic. We see that if an intervention cannot be sustained long-term, it has the greatest impact if it is imposed once infection levels have become large enough that there is an appreciable number of infections present. For minimising the total number infected it should start close to the peak so that there is no rebound once the intervention is stopped, while to minimise the peak prevalence, it should start earlier, allowing two peaks of comparable size rather than one very large peak. In populations with distinct subgroups, synchronized interventions are less effective than targeting the interventions in each sub-population separately. We do not attempt to clearly determine what makes an intervention sustainable or not. We believe that is a policy question. If an intervention is sustainable, it should be kept in place. Our intent is to offer insight into how best to time an intervention whose impact on society is too great to maintain.