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Register a new userSurvival Dynamical Systems for the Population-level Analysis of Epidemics
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Motivated by the classical Susceptible-Infected-Recovered (SIR) epidemic models proposed by Kermack and Mckendrick, we consider a class of stochastic compartmental dynamical systems with a notion of partial ordering among the compartments. We call such systems unidirectional Mass Transfer Models (MTMs). We show that there is a natural way of interpreting a uni-directional MTM as a Survival Dynamical System (SDS) that is described in terms of survival functions instead of population counts. This SDS interpretation allows us to employ tools from survival analysis to address various issues with data collection and statistical inference of unidirectional MTMs. In particular, we propose and numerically validate a statistical inference procedure based on SDS-likelihoods. We use the SIR model as a running example throughout the paper to illustrate the ideas.
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When effective medical treatment and vaccination are not available, non-pharmaceutical interventions such as social distancing, home quarantine and far-reaching shutdown of public life are the only available strategies to prevent the spread of epidemics. Based on an extended SEIR (susceptible-exposed-infectious-recovered) model and continuous-time optimal control theory, we compute the optimal non-pharmaceutical intervention strategy for the case that a vaccine is never found and complete containment (eradication of the epidemic) is impossible. In this case, the optimal control must meet competing requirements: First, the minimization of disease-related deaths, and, second, the establishment of a sufficient degree of natural immunity at the end of the measures, in order to exclude a second wave. Moreover, the socio-economic costs of the intervention shall be kept at a minimum. The numerically computed optimal control strategy is a single-intervention scenario that goes beyond heuristically motivated interventions and simple flattening of the curve. Careful analysis of the computed control strategy reveals, however, that the obtained solution is in fact a tightrope walk close to the stability boundary of the system, where socio-economic costs and the risk of a new outbreak must be constantly balanced against one another. The model system is calibrated to reproduce the initial exponential growth phase of the COVID-19 pandemic in Germany.
Understanding how to effectively control an epidemic spreading on a network is a problem of paramount importance for the scientific community. The ongoing COVID-19 pandemic has highlighted the need for policies that mitigate the spread, without relying on pharmaceutical interventions, that is, without the medical assurance of the recovery process. These policies typically entail lockdowns and mobility restrictions, having thus nonnegligible socio-economic consequences for the population. In this paper, we focus on the problem of finding the optimum policies that flatten the epidemic curve while limiting the negative consequences for the society, and formulate it as a nonlinear control problem over a finite prediction horizon. We utilize the model predictive control theory to design a strategy to effectively control the disease, balancing safety and normalcy. An explicit formalization of the control scheme is provided for the susceptible--infected--susceptible epidemic model over a network. Its performance and flexibility are demonstrated by means of numerical simulations.
In this paper, we introduce a novel modeling framework for incorporating fear of infection and frustration with social distancing into disease dynamics. We show that the resulting SEIR behavior-perception model has three principal modes of qualitative behavior---no outbreak, controlled outbreak, and uncontrolled outbreak. We also demonstrate that the model can produce transient and sustained waves of infection consistent with secondary outbreaks. We fit the model to cumulative COVID-19 case and mortality data from several regions. Our analysis suggests that regions which experience a significant decline after the first wave of infection, such as Canada and Israel, are more likely to contain secondary waves of infection, whereas regions which only achieve moderate success in mitigating the diseases spread initially, such as the United States, are likely to experience substantial secondary waves or uncontrolled outbreaks.
Antibodies, an essential part of our immune system, develop through an intricate process to bind a wide array of pathogens. This process involves randomly mutating DNA sequences encoding these antibodies to find variants with improved binding, though mutations are not distributed uniformly across sequence sites. Immunologists observe this nonuniformity to be consistent with mutation motifs, which are short DNA subsequences that affect how likely a given site is to experience a mutation. Quantifying the effect of motifs on mutation rates is challenging: a large number of possible motifs makes this statistical problem high dimensional, while the unobserved history of the mutation process leads to a nontrivial missing data problem. We introduce an $ell_1$-penalized proportional hazards model to infer mutation motifs and their effects. In order to estimate model parameters, our method uses a Monte Carlo EM algorithm to marginalize over the unknown ordering of mutations. We show that our method performs better on simulated data compared to current methods and leads to more parsimonious models. The application of proportional hazards to mutation processes is, to our knowledge, novel and formalizes the current methods in a statistical framework that can be easily extended to analyze the effect of other biological features on mutation rates.
Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control policies, but may be hindered by incomplete data in some regions of the world. Here we explore the opportunity of using proxy data or models for individual mobility to describe commuting movements and predict the diffusion of infectious disease. We consider three European countries and the corresponding commuting networks at different resolution scales obtained from official census surveys, from proxy data for human mobility extracted from mobile phone call records, and from the radiation model calibrated with census data. Metapopulation models defined on the three countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data well capture the empirical commuting patterns, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from both sources of data - mobile phones and census - are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, however preserving the order of infection of newly infected locations. Match in the epidemic invasion pattern is sensitive to initial conditions: the radiation model shows higher accuracy with respect to mobile phone data when the seed is central in the network, while the mobile phone proxy performs better for epidemics seeded in peripheral locations. Results suggest that different proxies can be used to approximate commuting patterns across different resolution scales in spatial epidemic simulations, in light of the desired accuracy in the epidemic outcome under study.
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